Particles 2009 - nanoparticles.org

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Particles 2009
Micro and Nano Encapsulation
11-14 July 2009
Holiday Inn Berlin-City West, Berlin, Germany
Graphic Courtesy of Jim Adair
TABLE OF CONTENTS
Sponsors
5
International Organizing Committee
7
Exhibitors
9
General Program Schedule
13
Map of Meeting Spaces
15
Technical Program
17
Abstracts
23
Speaker/Presenter Index
85
List of Preregistered Conferees
87
Notes
96
3
4
Sponsors
Co-Sponsored by:
Particles Conference
and
European Association of Pharma
Biotechnology
5
Sponsors
Corporate Sponsor
6
International Organizing Committee
J. M. Asua (Spain)
F. Boury (France)
D. Burgess (USA)
K. Caldwell (Sweden)
R. Duncan (UK)
M. El-Sayed (USA)
N. Garti (Israel)
K. Johnston (USA)
H. Kawaguchi (Japan)
J. H. Kim (Korea)
C. M. Lehr (Germany)
S. Margel (Israel)
H. Möhwald (Germany)
B. Moudgil (USA)
R. Mueller (Germany)
F. Nielloud (France)
T. Nilsen (USA)
7
D. Poncelet (France)
M. C. Roco (USA)
P. Rogueda (UK)
J. L. Salager (Venezuela)
R. Sharma (USA)
S. Simoes (Portugal)
P. T. Spicer (USA)
S. Svenson (USA)
J. Texter (USA), General Chai
8
Exhibitors
Beckman Coulter, Inc.
11800 S.W. 147th Avenue
Miami, FL 33196-2500, USA
Telephone: 1 800 526 3821
Fax: 1 800 232-3828
http://www.beckmancoulter.com
BüCHI Labortechnik AG
Meierseggstrasse 40
Postfach
CH-9230 Flawil 1
Switzerland
Telephone: +41 71 394 63 63
Fax: +41 71 394 64 64
http://www.buchi.com
9
Exhibitors
Distrilab Particle Technology
Olmenlaan 6C
3833 AV Leusden
The Netherlands
Telephone: +31 33 494 78 34
Fax: +31 33 432 14 41
http://www.distrioab.nl/
NanoSight Limited
Minton Park, London Road
Lysander Way
Amesbury, Wiltshire SP4 7RT
United Kingdom
Telephone: +44 (0)1980 676060
Fax: +44 (0)1980 624703
http://www.nanosight.co.uk/
10
Exhibitors
Surface Measurement Systems
5 Wharfside, Rosemont Road,
Alperton, Middlesex HA0 4PE
United Kingdom
Telephone: +44(0)208 795 9400
Fax: +44(0)208 795 9401
http://www.thesorptionsolution.com/
Surflay Nanotec GmbH
2 Centre One
Lysander Way
Salisbury, Wilshire SP4 6BU
United Kingdom
Telephone: +49 (0)30 6392 1764
Fax: +49 (0)30 6392 1767
http://www.surflay.com/
11
12
General Program Schedule
Registration – Registration Desk (inside Atrium, outside Grand Saal
entrance)
Saturday, July 11
(1800 – 2000) – Opening Reception, Mixer, & Exhibition (Atrium )
Sunday, July 12
(0830 – 1200) – General Session 1 (Grand Saal)
(1220 – 1400) – Luncheon & Exhibition (Atrium)
(1400 – 1730) – General Session 2 (Groser Saal)
(1800 – 2000) – Poster Session 1, Reception, & Exhibition (Atrium)
Monday, July 13
(1800 – 1930) – Poster Session 2, Reception & Exhibition (Atrium)
Tuesday, July 14
Conference Ends
13
14
Map of Meeting Spaces
All Conference activities take place in the Großer Saal and in the Atrium
on the ground floor just inside the main entrance and to the right of the
main lounge and bar area. Registration commences Saturday morning,
July 11th, at 9 am outside the Atrium. Registration opens at 8 am Sunday
– Tuesday, 12-14 July.
15
16
Technical Program
Sunday Morning, July 12, 2009
General Session 1 (Großer Saal)
Session Chair: Diane Burgess, University of Connecticut
0800 General Announcements
0835 1. Keynote - Denis Poncelet, Enitiaa, CNRS 6144 GEPHA, Nantes
Microencapsulation - Techniques and applications
0920 2. Rigoberto Advincula, University of Houston
Electropolymerizable organic and hybrid dendrimers: Packaging of encapsulated
nanoparticles and electro-optical materials
0950 Break
1020 3. Gleb Sukhorukov, University of London
Tayloring functions in microcapsules: Responsiveness and remote controlling
1050 4. Mathias Walther, Pfizer
Polymers for controlled release
1120 5. Stefaan De Smedt, University of Ghent
siRNA Dainecontaining nanoparticles: Stability of encapsulation and particle size
1150 6. Lars Daehne, Surflay Nanotec
Layer by layer technology in industrial applications
1200 End of Session
Sunday Afternoon, July 12, 2009
Session Chair: Gleb Sukhorukov, University of London
1400 7. Keynote - Gero Decher, University of Strasbourg
New nano bags and micro pouches
1445 8. Diane Burgess, University of Connecticut
Efficient and safe non-viral DNA delivery by anionic lipoplexes
1515 Break
1545 9. Andreas Fery, Univesity of Bayreuth
Mechanical characterization of polymeric microcapsules using atomic force microscopy
1615 10. Thomas Scheibel, University of Bayreuth
Spider silk for controlled drug delivery
1645 11. Alex M. van Herk, Eindhoven University of Technology
Synthesis of multicompartment latex particles
1715 12. Ren Xu, Beckman Coulter
Progress in nanomaterial characterization: Zeta potential determination
1730 - End of Session
Sunday Evening, July 12, 2009
17
Technical Program
Poster Session 1 (Atrium)
Session Chair: Melanie Martin, Particles Conference
1730-1930
13. Ilke Akartuna, ETH Zurich
Microcapsules from particle-stabilized emulsions
14. Erhan H. Altinoglu, The Pennsylvania State University
Multifunctional near infrared emitting calcium phosphate nanoparticles for simultaneous
diagnostic imaging and photodynamic therapy
15. Gema Antequera-Garcia, Universidade de Vigo
Low-fouling poly(N-vinyl pyrrolidone) capsules with engineered degradable properties
16. Cordin Arpagaus, Buchi Labortechnik AG
Nano spray dryer - Submicron particles of minimal powder quantities at high yields
17. Ricardo B. Azevedo, Universidade de Brasilia
Evaluation of itraconazole entrapped in nanospheres of PLGA for the treatment of
Paracoccidiodes Brasiliensis
18. Won San Choi, Korea Basic Science Institute
Hierarchically nanostructured particles as a nanoreactor for synthesis of core-shell
particles
19. Andreas L. Christensen, University of Copenhagen
Quantification of the encapsulation efficiency in single small unilamellar vesicles and
investigation of vesicle-DNA interactions
20. Sune M. Christensen, University of Copenhagen
Single vesicle encapsulation and fusion: The design of an attofluidic biochip
21. Liesbeth J. De Cock, Ghent University
Application of polyeledctrolyte capsules in the domain of tissue-engineering as carriers
for growth factor delivery
22. Loretta L. del Mercato, Philipps Universitat Marburg
Uptake of colloidal polyelectrolyte multilayer capsules by living cells
23. Jiri Dohnal, ITC-Prague
Use of drop-on-demand nozzle for microparticle production
24. Tristan Doussineau, Friedrich Schiller University
Fluorescent ratiometric pH-nanosensors for biodiagnosis applications
25. Philipp Erni, Firmenich SA
Interfacial rheology of surface-active biopolymers: Gum arabic vs. hydrophobically
modified starch
26. Chiara Giannachi, Bracco Imaging SpA
Novel paramagnetic mixed micelles as potential MRI contrast agents
27. Kay Hettrich, Fraunhofer Institute for Applied Polymer Research, Golm
Microencapsulation of biological objects with cellulose sulfate
28. Chutima Jantarat, Prince of Songkla University
Molecularly imprinted nanoparticle-on-microsphere chiral cinchona-polymers for the
enantioselective-controlled delivery of racemic omprazole
29. Katsumi Kamegawa, NIAIST, Saga, Japan
Production of hollow carbon microparticles from biomass resources
30. Vanja Kokol, University of Maribor
Polyelectrolyte nano-assembled microcapsules for biosensing of glucose in human sweat
31. Pavel Kovacik, Institute of Chemical Technology Prague
18
Technical Program
Synthesis and controlled release characteristics of hollow SiO2 microparticles
32. Seta Küpcü, University of Natural Resources and Applied Life Sciences â€“ BOKU
Nanobiotechnological potential of S-layer coated liposomes
33. Jongwi Lee, Chung-Ang Universsity
Electrohydrodynamic jetting of polymers using co-axial nozzles
34. Jongwi Lee, Chung-Ang Universsity
Polymer-directed crystallization of atorvastatin
35. Dennis Lensen, University of Nijmegen
Multi-functional poly urea formaldehyde capsules
36. Iratxe Madrietia-Pardo, INASMET-TECHNALLIA
Double controlled release from hybrid materials containing microspheres and hydrogels
in vivo
37. Isabel M. Martins, University of Porto
Microencapsulation by coacervation of biodegradable polymer with thyme oil
38. Olga Mykhaylyk, Technische UniversitÃ¤t MÃ¼nchen
Magnetic nanoparticles for gene delivery: Some determinants of efficient delivery vectors
Monday Morning, July 13, 2009
Session Chair: Cornelia Keck, PharmaSol GmbH
0835 39. Keynote - Ronald Versic, R.T. Dodge
Industrial encapsulation processing
0920 40. Ian Marison, Dublin City University
Liquid-core micro and nanocapsules for the extraction of drugs and pesticides/herbicides
0950 Break
1020 41. Bruno De Gheest, University of Ghent
Degradable polyelectrolyte capsules for biomedical applications
1050 42. Christian Quellet, Givaudan
Fragrance encapsulation in micro and nanoparticles
1120 43. Thorsten Brandau, BRACE GmbH
Manufacturing microcapsules for advanced materials
1150 End of Session
Monday Afternoon, July 13, 2009
Session Chair: Thorsten Brandau, BRACE GmbH
1400 44. Keynote - Helmuth Möhwald, Max Planck Institute of Colloids and Interfaces
Microcapsules with controlled and remote release
1445 45. Cornelia Keck, PharmaSol GmbH
Lipid nanoparticles for the delivery of actives in pharma, cosmetics and consumer care
19
Technical Program
1515 Break
1545 46. Gulden Yilmaz, Wageningen University and Research Centre
One processing technology - Variable applications
1615 47. Jean Antoine Meiners, MCC s.a.
Particle engineering to design protection and release of microencapsulated bioactives
1645 48. Berit L. Strand, Norwegian University of Science and Technology
Encapsulation with alginates
1715 - End of Session
Monday Evening, July 13, 2009
Poster Session 2 (Atrium)
Session Chair: Melanie Martin, Particles Conference
1730-1930
49. Lise Junker Nielsen, University of Southern Denmark
Peptide mediated delivery of opticdal nanosensors into S. cerevisaes
50. Tsutomu Ono, Okayama University
Development of nanoparticles containing photosensitizer with diblock copolymer for
photodynamic therapy
51. Veli Cengiz Ozalp, University of Southern Denmark
Aptamer embedded polyacrylamide nanoparticles used as nanosensors for metabolite
detection in vivo
52. Isabel Pastoriza-Santos, Unidad Asociada CSIC-Universidade de Vigo
Encapsulation of gold nanparticles in a PNIPAM microgel: Nanoreactors and molecular
traps for SERS
53. Rafael Piñol, Universidad de Zaragoza
Smectic polymer vesicles
54. Rafael Piñol, Universidad de Zaragoza
Multi-stimuli responsive poly(4-vinyl pyridine) nano- and microspheres as candidates for
remote controlled drug delivery
55. Clive A. Prestidge, University of South Australia
Hybrid nanostructured microcapsules composed of silica nanoparticles and lipid
emulsions: Encapsulation and delivery of poorly soluble drugs
56. Pilar Rivera Gill, Philipps University of Marburg
Delivery of microcontainer with active components to cells
57. Sofia N. Rodrigues, University of Porto
Synthesis of polyurethane-urea microcapsules with perfume for textile application
58. Virginia Sáez-Martínez, INASMET-TECNALIA
Controlled release studies of dexamethasone from nanometric hydrogels for ophthalmic
applications
59. Yuika Saito, Osaka University
Photopolymerization of fullerenes encapsulated in SWCNT
60. M. Magdalena Sánchez-Navarro, INESCOP
Melamine-formaldehyde microcapsules containing eucaliptus essential oil for footwear
applications
61. Gitte Sørensen, Danish Technological Institute
Slow release of biocide from silica microparticles in wood paints
20
Technical Program
62. Antonio Stocco, UniversitÃ© Paris-Sud
Silica nanoparticles at air-water interfaces
63. Antonio C. Tedesco, Universidade de Sao Paulo
In vitro cellular phototoxicity of nanocapsules containing a metallophthalocyanine on
B16-F10 Melanoma cells
64. João Tedim, University of Aveiro
Layered double hydroxide nanocrystals loaded with exchangeable anions for controlled
corrosion protection
65. John Texter, Eastern Michigan University and Max Planck Institute, Golm
New di-stimuli responsive di-hydrophilic diblocks for chemical delivery
66. Benjamin Thierry, University of South Australia
Hybrid plasmonic colloidal nanostructures
67. Doris Vollmer, Max Planck Institute for Polymer Research, Mainz
Mechanical properties of single hollow silica particles
68. Dennis M. Vriezema, Encapson BV
Encapsulation as a business
69. Yanhong Wen, University of Copenhagen
Development of activated spherical particles as a scaffold for tissue regeneration
70. Ren Xu, Beckman Coulter, Inc.
Development of amorphous drug nanoparticles by NovaSperse™ technology
71. Ales Zadrazil, Institute of Chemical Technology Prague
Synthesis and controlled release from polymer microsponges
Tuesday Morning, July 14, 2009
Session Chair: Pei Li, Hong Kong Universityof Science and Technology
0830 General announcements; presentation of PlasmaChem Prize
0835 72. Harm-Anton Klok, EPFL
Facile and convergent synthesis of polymer-coated gold nanoparticle libraries
0905 73. Angus Johnston, University of Melbourne
Assembly of bioinspired, nanoengineered materials for targeted drug delivery
0935 74. Anna Musyanovych, Max Planck Institute for Polymer Research, Mainz
Formation of smart nanocapsules for defined slow or sudden release
1005 Break
1030 75. Edwin Donath, University of Leipzig
Engineering particles with biointerfaces employing viral architectures
1100 76. Dmitry Shchukin, Max Planck Institute of Colloids and Interfaces
Nanocontainers with controlled permeability for feedback active coatings
1130 77. Heidi Johnsen, SINTEF
Emulsion based encapsulation
1200 End of Session
21
Technical Program
Tuesday Afternoon, July 14, 2009
Session Chair: John Texter, Eastern Michigan University and Max Plamck Institute for
Colloids and Interfaces
1400 78. Pei Li, Hong Kong University of Science and Technology
Amphiphilic core-shell particles in advanced waste water treatment technology
technology
1430 79. Simona Margutti, Fraunhofer IAO, Stuttgart
Encapsulation approaches in advanced display technology
1500 Break
1530 80. Matthieu Bedard, Queen Mary College
Optically addressable microcapsules
1600 81. Keynote - Jim Adair, Penn State University
Inorganic encapsulation of organics for imaging and delivery
1645 Panel Discussion - Diane Burgess, Rainer Mueller, Denis Poncelet, and Ronald
Versic
Discussion of Conference Issues
1715 End of Conference
22
Abstracts
General Session 1 – Keynote Paper
MICROENCAPSULATION : METHODES AND AND TECHNOLOGIES,
Denis Poncelet, ENITIAA, UMR CNRS 6144 GEPEA, Rue de la
Géraudière, BP 82225, 44322 Nantes Cedex 3, France;
[email protected]
1
Biological cells are an incredible system allowing life to develop by immobilizing,
protecting, controlling the transfer, structuring and functionalising the actives.
Researchers and engineers tends to mimic them by producing microcapsules with already
a large range of applications and event more potential ones, in all domains of our daily
life. Face to the diversity of applications and the multidisciplinary aspects of the
microencapsulation, it is quite difficult to understand how to select the most adequate
method in function of a specific request and to find optimum conditions to develop a
process. The talk will then cover both the understanding of why making encapsulation,
which questions must be introduced to select a method and how to classify the different
technologies.
General Session 1 – Invited Paper
ELECTROPOLYMERIZABLE ORGANIC AND HYBRID DENDRIMERS:
PACKAGING OF ENCAPSULATED NANOPARTICLES AND
ELECTRO-OPTICAL MATERIALS
Rigoberto Advincula, Department of Chemistry and Department of
Chemical Engineering, University of Houston, Houston, Texas, USA 77204;
[email protected]
2
Organic polymer and hybrid materials are of high interest for investigating structureproperty relationships that extends from composite materials to core-shell nanoparticle
systems. In particular, the utilization of dendrimeric systems and their ability to have
various levels of functionality with the core, generation, or peripheral group makes them
ideal for hybrid material system investigations. The synthesis of organic dendrimers
involves either a convergent or divergent approach. The key strategy involves a selective
exponential growth of the functionality both at the branching point and at the periphery.
In this work we demonstrate the two possibilities of synthetic routes for packaging and
isolating nanoparticles through the electropolymerizability of the corresponding
peripheral groups. This involves the synthesis of dendrons that can act as capping agents
or shell layers to package or host nanoparticles (metal or semiconductor) and their
corresponding electro-optical properties. On the other hand the use of existing dendrimers
such as PAMAM enable the hosting of catalytic nanoparticles capable of selective
adsorption properties on electrodes. The ability to simultaneously target encapsulation
simultaneous with the intrinsic hybrid electro-optical property is important. Lastly, the
electropolymerizability of the peripheral groups make them ideal for specific applictions
as nano-objects, photovoltaic, and sensor devices.
23
Abstracts
General Session 1 - Invited Paper
TAILORING FUNCTIONS IN MICROCAPSULES: RESPONSIVENESS
AND REMOTE CONTROLLING
Gleb Sukhorukov, School of Engineering and Materials Science, Queen
Mary University of London, Mile End Road, E1 4NS, London, United
Kingdom; [email protected]
3
Layer-by-layer assembled capsules are owing to their ability to encapsulate a wide range
of chemicals, for their permeability to be modified and their responsiveness to different
factors and functionalities to be tailored in one capsule entity. Composite
polymer/nanoparticles capsules with tailored functions represent a novel type of
microcontainers with multifunctional properties. These capsules are made by layer-bylayer adsorption of oppositely charged polyelectrolytes on colloidal template particles,
including emulsions, drug nanoparticles and gas bubbles, of 0.05 – 20 µm diameter with
sequential removal of the template core. A great variety of materials including synthetic
and natural polyelectrolytes, proteins, multivalent ions, organic nanoparticles, lipids were
used to build walls of hollow capsules. The possibility of tailoring different
functionalities, impregnating inorganic and organic substances both inside capsule
volume and in polyelectrolyte shell, controlled release of encapsulated material provided
continuous scientific and industrial interest for employing capsules as microcontainers
and microreactors. Smart polymers involved in capsule build-up exhibit reversible
sensitivity to environmental conditions, such as temperature, pH, ions, etc. Inorganic
nanoparticles incorporated to polyelectrolyte shell makes possible the remote activated
release by ultrasound or infrared radiation as well as to guided by magnetic field.
Multifunctional (several properties in one entity) capsules make them unique for many:
controlled drug delivery, absorbents for solvent extractions, separation processes, sensors
or actuators. The possibilities for practical applications on living systems are illustrated
on cell culture level. Current research leads to the fabrication of carriers with remote
guiding and activation by optical, magnetic and ultrasound addressing, what envisages
unique applications as multifunctional biomaterials in-vivo. Submicron sized capsules are
good model to mimicking bio-chemical processes in a confined geometry imitating cell
organelles, whilst delivered inside cell and tissues the capsules could serve as
intracellular reporter or enzymatic reactor.
POLYMERS FOR CONTROLLED DRUG RELEASE APPLICATIONS
- USING FILM MICROSTRUCTURE TO CONTROL PERFORMANCE
Mathias Walther, Pfizer Ltd, Sandwich, Kent, CT13 9NJ, United Kingdom;
[email protected]
4
Polymers are routinely used as coating materials to control drug release from
multiparticulate pharmaceutical dosage forms such as microspheres, pellets, granules etc.
The need to deliver drugs with a wide range of physico-chemical properties and specific
pharmaco-kinetic treatment targets has resulted in the development of various approaches
that utilize available pharmaceutical grade polymers and create novel functionality by
combining materials with different properties. This presentation provides an overview
with practical examples to illustrate different strategies that are routinely used to adjust
24
Abstracts
coating functionality. In particular, the use of polymer blends is discussed as it offers
major advantages, including: (i) facilitated adjustment of desired drug release patterns,
mechanical properties and drug release mechanisms, (ii) improved film formation and
storage stability, and (iii) the possibility to develop novel strategies for site specific drug
delivery within the gastro intestinal tract (e.g., colon targeting). The microstructure of
the film coat is critical to control performance and can be affected by formulation
variables and materials properties as well as the manufacturing process. Consequently,
the increased complexity of such systems makes optimization and scale-up more
challenging. A fundamental understanding of the underlying drug release mechanisms
coupled with an insight into the film microstructure is highly desirable to render the
optimization of this type of advanced delivery systems more efficient.
siRNA CONTAINING NANOPARTICLES: STABILITY OF
ENCAPSULATION AND PARTICLE SIZE
Kevin Buyens, Kevin Braeckmans, Niek N. Sanders, Joseph Demeester and
Stefaan C. De Smedt, Ghent Research Centre on Nanopharmacy,
Department of Pharmaceutics, University of Ghent, Harelbekestraat 72, 9000
Ghent, Belgium; [email protected]
5
A lot of efforts are currently made in the development of nano-scaled carrier systems that
can guide siRNA molecules to their target cells after intravenous injection. One of the
main issues in this research is the integrity of the siRNA containing nanoparticles in the
blood stream. The integrity of the nanoparticles comprises both the particle size and the
stable encapsulation of the siRNA. Techniques currently available for studying the
disassembly and size distribution of siRNA containing nanoparticles are time-consuming
and incompatible with biological fluids. First we developed a fluorescence fluctuation
spectroscopy (FFS) based method which allows to monitor the integrity of siRNA-carrier
complexes in less than one minute in complex biological media and at very low siRNA
concentrations. Second, while the size distribution of the complexes can be easily
measured in a clear dispersion by dynamic light scattering or electron microscopy, it
cannot be measured in more complex biological media such as plasma or whole blood,
which contain all kinds of interfering components. To address this issue, we have
developed a novel technique, based on single particle tracking (SPT) microscopy, for
studying the size distribution (and aggregation) of nanoscopic drug complexes in
biological fluids. For stabilization of the particle size of cationic lipid based
nanoparticles, inclusion of lipids conjugated with PEG are widely used to sterically
hinder aggregate formation. We have demonstrated that in order to obtain remaining
siRNA complexation to the cationic liposomes, effective encapsulation inside the
liposome, or in between lipid multilayers is required, since siRNA electrostatically bound
to the outer side of the liposomes is quickly pushed away by the ubiquitous albumin
molecules in blood which leads to siRNA degradation and loss of effectiveness.
Formation of siRNA protecting multilayers is hindered by inclusion of PEG-lipids, a Figure 12
hurdle that needs to be overcome by either post-insertion of the PEG-lipid into multilayer
containing siRNA-liposome complexes, or by efficient encapsulation of the siRNA inside
the aqueous core of the PEGylated liposome.Size stabilization in buffer can be easily
achieved by inclusion of minor percentages (~1%) of PEG-lipids. In whole blood
however, we demonstrate that much higher percentages of PEG-lipids (5-10%) are
25
Abstracts
required to achieve size stabilization. The latter being a fact that has not been taken into
account sufficiently up until now, because of the lack of a suitable technique to study the
aggregation phenomena in whole blood.In our work we demonstrate that assaying the
physicochemical properties of siRNA encapsulating nanoparticles should always be
carried out in the biological media they are designed to be employed in. Two novel
microscopy based methods were developed that enable such characterization in biological
fluids like serum, plasma or even whole blood.
General Session 1 – Exhibitor Focus Paper
LAYER BY LAYER TECHNOLOGY IN INDUSTRIAL APPLICATIONS
Lars Dähne, Gabriella Egri, Jing Kang, Barbara Baude, Surflay Nanotec
GmbH, [email protected]
6
Since the development of the LbL technology by Gero Decher et.al. a currently
increasing scientific community was developing a huge amount of possible solutions and
applications by means of LbL both on planar surfaces and colloidal templates. However,
despite of this high future potential only very few technical applications are known up to
now. Our company is trying to bring some of the most promising developments to the
market but the traditional industry is rather defensive about this technology because of
questions about biocompatibility, stability, price, permeability etc. We will present three
actual developments of LbL-coated particles of our company and highlight the possible
advantages and also drawbacks of these particles against traditional beads. These
developments are in the field of
- none-sedimenting 3 µm air-filled beads (bubbles)
- DNA-sensitive beads with high hybridization efficacy
LbL modified bioseparation materials
NEW NANO BAGS AND MICRO POUCHES
Gregory F. Schneider, Vladimir Subr, Karel Ulbrich, and Gero Decher;
Centre National de la Recherche Scientifique (CNRS UPR 22), Institut
Charles Sadron, 23 rue du Loess, F-67034 Strasbourg, France; Université de
Strasbourg, 1 rue Blaise Pascal, F-67008 Strasbourg-Cedex, France; and
Institute of Macromolecular Chemistry, Heyrovsky Sq. 2, 162 06 Prague 6,
Czech Republic; contact: [email protected]
7
Materials Science has always been driven by the desire to transform matter into something more useful, which is typically also thought to be more valuable. One of the important tools for creating order is molecular self-organization based on molecules which
undergo molecular self-assembly. However, even simple devices are often multimaterial
composites with a complex and sometimes even hierarchical structure. It is evident that
basic self-assembly methods will not be able to address molecular organization at this
level and, as a consequence, multistep assembly procedures will need to be employed for
the (nano)fabrication of such materials or devices. Layer-by-layer (LbL) assembly has, in
the last years, developed into a method, which begins to make it possible to construct
multimaterial soft-matter devices by rational design. The examples of hybrid
26
Abstracts
nanomaterials discussed at this conference are new cytotoxic stealth nanoparticles made
by LbL-deposition (I) and “nanobags” which are made by a process based on flocculation
(II).
I.) We report on a highly versatile nanoparticle-based core/shell drug delivery system
consisting of cytotoxic stealth carrier particles. Their multifunctional shells, mandatory
for addressing different diagnostic/treatment requirements, are constructed by robust
electrostatic and covalent layer-by-layer assembly leading to nanoparticles with
multilayer shells that combine all of the following properties: (i) a small size distribution
of the nanoparticle carrier, (ii) a high stability in physiological media, (iii) attachment of
a pro-drug in covalent form and thus a low toxicity of the carrier system, (iv) the triggered release and activation of the drug only after endocytosis and enzymatic cleavage,
and (v) “stealthiness” and thus protection against uptake by macrophages.
II.) The control of simple parameters involved in the process of classic bridging flocculation allows the preparation and fine-tuning of a new class of hybrid nanomaterials with
respect to size, composition, and morphology. The resulting nanoparticle-filled “nanobags” are obtained in aqueous suspension by mixing three basic components, a polyelectrolyte, a multivalent ion, and nanoparticles in different ratios. The size range in which
nano- and micropouches can be prepared seems to start at about 25 nm; these are oligonanoparticle aggregates whose size are clearly related to the size of the nanoparticles
themselves and seem to extend up to about 5 µm. By controlling the stoichiometric
balance between the global number of positive and negative charges on the polycation
and on the multivalent anion and by controlling the absolute concentrations and the
ratios, namely of the polyelectrolyte and the nanoparticles, one has access to a wide range
of different nanopouch morphologies and compositions.
EFFICIENT AND SAFE NON-VIRAL DNA DELIVERY BY ANIONIC
LIPOPLEXES
Charudharshini Srinivasan, Mamta Kapoor and Diane J. Burgess;
Department of Pharmaceutical Sciences, 69 North Eagleville Road, Unit
3092, University of Connecticut, Storrs, CT 06269, USA.
[email protected]
8
The success of gene delivery depends on efficient cellular delivery of DNA-based
therapeutics using physiologically safe vectors. Recently a lot of attention has been given
to cationic lipids and polymers as well as polymeric nanoparticles non-viral vectors. In
an effort to improve the safety of non-viral vectors the use of an anionic lipid carrier
system, comprising divalent cation mediated, DNA and anionic liposome complexes
(lipoplex), is explored in this study. Anionic liposomes comprised of mixtures of
anionic/zwitterionic lipids ((DOPG/DOPE) at varying molar ratios (10/90 to 50/50)) were
prepared by rotary evaporation method. The anionic lipoplexes were formed by
complexing the liposomes with plasmid DNA (pEGFP) and a divalent cation, Ca 2+.
Lipofectamine 2000 was used as a control. Transfection was conducted in CHO-K1 cells
in presence of serum and quantitative EGFP expression analysis was conducted by
spectrofluorimetric analysis in a FLUOstar Optima microplate reader. MTT (3-[4,5-
27
Abstracts
dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) colorimetric assay was
performed to determine toxicity. Particle size analysis, zeta potential, gel electrophoresis,
transmission electron microscopy and confocal studies were performed for liposomes and
lipoplex characterization studies. DNA molecules formed stable complexes with anionic
liposomes and optimum transfection efficiency occurred at 15 – 20 mM Ca 2+ and a 20/80
(anionic/zwitterionic) lipid molar ratio with lipid/DNA ratios at 15 – 20 µg/0.8 µg. The
transfection efficiency of anionic lipoplex (~78% ) was comparable to the cationic
Lipofectamine2000/DNA complex (~68%). Lipofectamine 2000/DNA complex resulted
in high toxicity compared to anionic lipoplexes. Cell viability of anionic lipoplex (~93%)
was much higher than the Lipofectamine2000/DNA (~35%). Particle size analysis, gel
electrophoresis, transmission electron microscopy and confocal studies assisted in
characterization of optimized anionic lipoplex formulations. The anionic lipoplexes
labeled with rhodamine-PE to track the lipoplexes intracellularly and nucleus stained
with SYTO-45 blue nuclear stain revealed that the lipoplexes were localized at the perinuclear region following 3 h incubation in CHO-K1 cells. The anionic lipoplexes appear
to be a suitable candidate for DNA delivery with comparable transfection efficiencies to
cationic lipids and significantly less cytotoxicity.
MECHANICAL CHARACTERIZATION OF POLYMERIC
MICROCAPSULES USING ATOMIC FORCE SPECTROSCOPY
Andreas Fery, Department of Physical Chemistry II, University of Bayreuth,
Universiteatsstr. 30, D95444 Bayreuth, Germany;
[email protected]
9
Mechanical properties of microcapsules govern (mechanical) stability, deformation
behavior and influence adhesion. Thus techniques that allow for characterization of
individual microcapsules are of interest for fundamental science just as well as for
various fields of application. The talk summarizes results obtained from AFM-based
single-capsule deformation experiments with a focus on stimulus responsive systems like
polyelectrolyte multilayer shells. Deformation properties can be investigated in aqueous
environment and parameters like pH, salt concentration or temperature can be varied in
situ. Continuum mechanical modeling can explain the observed deformation forces and
provide guidelines for achieving responsive capsule systems with tailored mechanical
properties. Especially for more complex systems like Pickering emulsion droplets or gas
filled particles (microballoons), complementary information on shape changes in various
stages of deformation is essential. This can be achieved by combination of AFM with
optical techniques like micro-interferometry or fluorescence microscopy. We discuss
findings on these systems and give an outlook on future perspectives.
SPIDER SILK FOR CONTROLLED DRUG DELIVERY
Andreas Lammel1, Martin Schwab3,Gerhard Winter3, Thomas Scheibel2;
1
Lehrstuhl Biotechnologie, Lichtenbergstraße 4, Technische Universität
München, D-85747 Garching, Germany; 2Lehrstuhl Biomaterialien,
Universitätsstraße 30, Universität Bayreuth, D-95440 Bayreuth, Germany;
10
28
Abstracts
3
Department of Pharmacy, Pharmaceutical Technology and
Biopharmaceutics, Ludwig-Maximilians-Universität, D-81377 Munich,
Germany; [email protected]
Biological materials often exceed the characteristics and properties of man-made ones.
One well-known example is spider silk with superior mechanical properties such as
strength and toughness. Most spider silks are used for building the web, which reflects an
optimized trap for flying prey. Already thousands of years ago the excellent mechanical
properties and low immunogenicity of spider webs have been acknowledged by men,
employing them as fishing nets or as wound closure devices. However, large-scale
farming of spiders has been quickly abandoned due to the territorial and cannibalistic
behavior of most spiders. In order to avoid such complication, we developed a bioinspired system using bacteria as production hosts which produce silk proteins mimicking
the natural spider silks. Our engineered spider silk proteins can be processed into fibers,
but also into particles which can be used as drug carriers. Silk particles are colloidaly
stable in solution and can be efficiently loaded. In vitro release studies showed that
constant release rates at physiological conditions can be realized for a period of two
weeks. Silk particles have a huge potential for diverse applications with desired
controlled release from biocompatible carriers.
SYNTHESIS OF MULTICOMPARTMENT LATEX PARTICLES
Alex M. van Herk*, Syed Imran Ali, Hans Heuts, Eindhoven University of
Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands;
[email protected]
11
In the field of encapsulation of many types of particles like pigments, fillers and clay
particles [1,2] tremendous progress has been made and applications of encapsulated
inorganic particles are known, for example in car coatings. Core-shell latex particles are
applied for many decades. Encapsulation of all kind of materials like pigment particles,
filler particles and magnetic particles is known. A new challenge is in the encapsulation
of clay platelets striving towards a high aspect ratio of the resulting nanostructured
particles. One is struggling with surface tensions there and the thermodynamic driving
force to small surface area. Similar problems exist in the field of vesicle polymerization
[3]. After careful studies it turned out to be very difficult to produce a thin wall of
polymer inside the hydrophobic domain of the vesicle double layer. The most common
structure produced is that of the parachute, a latex particle connected to the vesicle
structure. Apparently only with strong covalent bonds between the surfactant and the
polymer one is able to produce hollow particles through vesicle polymerization. The field
of vesicle polymerization opens many possibilities to produce many different and
interesting new nanostructured particles. Specialty applications like intraocular eye lenses
bases on transparent latices are showing the enormous potential of nanocomposites in the
area of specialties [4]. In this paper it will be shown that many different
multicompartment structures can be produced while applying the general principles of
thermodynamics and kinetics in emulsion polymerizations. One example are the so-called
nanobottles where a hollow structure is combined with a latex particle making a lid for
the ‘nanobottle’ (see Figure 1). The authors wants to ackowledge Dirk-Jan Voorn, Martin
29
Abstracts
Jung, Jens Pusch, Jens Hartig and Marshall Ming for their important contributions on the
development of this research line
1. D.J. Voorn, W. Ming, A.M. van Herk, Clay Platelets Encapsulated Inside latex
Particles, Macromolecules 2006, 39, 4654-4656
2. A.M. van Herk and A.L. German, "Microencapsulated pigments and fillers",
contribution to the book 'Microspheres, Microcapsules & Liposomes', vol 1 : Preparation
& Chemical Applications, Citus Books, London , ed Prof. R Arshady (1999)
3. M. Jung, D.H.W. Hubert, P. Bomans, P.M. Frederik, A.M. van Herk, A.L. German
"A Topology map for novel vesicle-polymer architectures" Advanced Materials 12 2000
210-213
4. J. Pusch, A.M. van Herk Emulsion polymerization of novel transparent latices with
pulsed electron beam initiation Macromolecules 38 2005, 6939-6945
Figure 1. One of a kind nanobottle produced in vesicle polymerization (normal particles
look more spherical).
General Session 2 – Exhibitor Focus Paper
ROGRESS IN NANOMATERIAL CHARACTERIZATION: ZETA
POTENTIAL DETERMINATION
Ren Xu, Beckman Coulter Inc., Miami, FL, USA; [email protected]
12
Zeta potential measurement of particles in suspension is a very important research tool
and quality control means for dispersion stability and product performance of nano or
submicron particulate materials and has been transformed from an explorative tool to a
must-have means in recent years. There are two technologies that are commonly used for
zeta potential measurement, i.e., electrophoretic light scattering (ELS) and acoustic. The
ELS technology produces accurate and high resolution results for particles in either
aqueous or non-aqueous suspensions. However, its current applications are limited to
dilute samples due to the conventional optical arrangement. It is important to measure
zeta potential of particles in their native environment, which is often a concentrated
suspension, since zeta potential of particles is a property of the particles as well their
environment. Improper dilution often produces correct but irrelevant information. In this
presentation, a patented technology (FST) used for ELS measurement will be introduced.
In the FST technology, measurements are performed on particles near a transparent
30
Abstracts
electrode therefore avoiding multiple scattering and scattering attenuation due to high
solid concentration. The knowledge of surface charge (zeta potential) of solid surfaces,
such as engineered membranes, fabrics, and celluloses, is important to understand,
predict or modify surface properties of these materials. However, there have been few
effective ways to measure surface charge of flat surface immersed in liquid. A new
electroosmotic probing method to determine surface charge of flat surface in liquid will
be described.
Poster Session 1 – Contributed Paper
MICROCAPSULES FROM PARTICLE-STABILIZED EMULSIONS
I. Akartuna, P. N. Sturzenegger, U. T. Gonzenbach, E. Tervoort, A. R.
Studart, L. J. Gauckler; Department of Materials, ETH Zürich, WolfgangPauli-Strasse 10, 8093 Zurich, Switzerland; [email protected]
13
Microencapsulation holds the potential to overcome a number of challenges in
technology ranging from targeted administration of chemicals over controlled release to
screening active agents from environmental influence. Although a considerable variety of
surfactant and polymer based encapsulation methods are already developed to solve
specific problems, a platform technology for microencapsulation does still not exist.
Particle-stabilized systems are potential candidates to provide new solutions in the field
of micro-encapsulation due to the great freedom in the selection of materials and their
outstanding properties. Here we present a processing route for the fabrication of
microcapsules from particles via emulsion templating. The assembly of particles at the
oil-water interface is induced by the in situ hydrophobization of the particle surface
through the adsorption of short amphiphilic molecules. The adsorption of particles at the
interface leads to highly stable emulsions with tailorable microstructures. Dilution of
these emulsions results in wet capsules that can be harvested into hollow capsules upon
drying. Organic binders are used to increase the mechanical integrity of the capsule shell.
This process allows the fabrication of capsules with controlled sizes and compositions
using wide variety of colloidal particles. These solid-coated microcapsules are expected
to offer several advantages compared to amphiphilic and polymeric vesicles such as
mechanical and chemical robustness, temperature resistance and better environmental
compatibility.
MULTIFUNCTIONAL NEAR INFRARED EMITTING CALCIUM
PHOSPHATE NANOPARTICLES FOR SIMULTANEOUS DIAGNOSTIC
IMAGING AND PHOTODYNAMIC THERAPY
E. İ. Altınoğlu*, T. Russin#, B.M. Barth+, S. Saravanan+, P. C. Eklund*#, and
J. H. Adair*, *Department of Materials Science and Engineering, #Department
of Physics, +Hershey Medical Center, Department of Pharmacology,
The Pennsylvania State University, University Park, PA 16802, USA;
[email protected]
14
Simultaneous early detection and treatment are crucial elements for the timely diagnosis
and successful eradication of all cancers, but are limited by the sensitivity and efficacy of
31
Abstracts
current imaging and therapeutic methodologies, respectively. Thus, much interest has
initiated in both near infrared (NIR) contrast agents for sensitive, deep tissue imaging,
and non-toxic photosensitizers for noninvasive, localized, molecular-scale photodynamic
therapy. The full potential of such concurrent early stage diagnosis and treatment lies in
the ability to engineer multifunctional vectors with unique optical properties that can
penetrate early-stage lesions with a high-level of targeted specificity and maximum
photostability while simultaneously prompt a localized photodynamic response to initiate
cell death. Here we report the synthesis of bioresorbable calcium phosphate nanoparticles
(CPNPs) which encapsulate molecules of the NIR fluorophore indocyanine green (ICG)
for use as a fluorescent photosensitizer agent for synchronized real-time, deep-tissue
imaging and therapy. These ICG-CPNPs demonstrate exceptional colloidal and optical
characteristics. Suspensions consisting of 16 nm average diameter particles are
colloidally stable in physiological solutions (phosphate buffered 0.15 M saline (PBS), pH
7.4) with polyethylene glycol (PEG) surface passivation. The doped CPNPs exhibit
significantly greater intensity at the maximum emission wavelength relative to the free
constituent fluorophore, consistent with the multiple molecules encapsulated per particle.
The quantum efficiency per molecule of the ICG-CPNPs is 200% greater at 0.049±0.003
over the free fluorophore in PBS. Photostability based on fluorescence half-life of
encapsulated ICG in PBS is 500% longer under typical clinical imaging conditions
relative to the free dye. Furthermore, the ex situ generation of singlet oxygen (1O2) from
these multifunctional vectors is matched by exceptional in vivo photodynamic responses.
PEGylated ICG-CPNPs accumulate in solid, 5 mm diameter xenograft breast
adenocarcinoma tumors via enhanced retention and permeability (EPR) within 12 h after
systemic tail vein injection in a nude mouse model. Moreover, after a single localized
dosage of 785 nm light (50 J/cm2), tumor growth is completely arrested over 36 days,
whereas untreated controls grow to over 10 times their initial size. Experimental ex situ
data are also used to theoretically model clinical deep-tissue imaging and therapeutic
performances with NIR signals detectable at depths up to 10 cm and therapeutic
photodynamic responses initiated from 7 cm in breast tissue. With these superior optical
properties, inherent singlet oxygen generation, and promising in vivo photodynamic
performances, ICG-CPNPs can impart an improved parallel approach to sensitive earlystage diagnosis and site specific therapy.
LOW-FOULING POLY(N-VINYL PYRROLIDONE) CAPSULES WITH
ENGINEERED DEGRADABLE PROPERTIES
Gema Antequera-García,# Cameron R. Kinnane,† Georgina K. Such,† Yan
Yan,† Sarah J. Dodds,† Luis M. Liz-Marzan,# and Frank Caruso†*
#
Colloid Chemistry Group, Departamento de Química Física and Unidad
Asociada CSIC, Universidade de Vigo, Vigo 36310, Spain; †Centre for
Nanoscience and Nanotechnology, Department of Chemical and
Biomolecular Engineering, The University of Melbourne, Parkville, Victoria
3010, Australia; Email: *[email protected]; #[email protected]
15
Hollow polymer capsules have generated significant scientific and technological interest
over the past decade because of their promise for application as microreactors, specific
targeting and sensors. To date, the most versatile method used for assembling such
32
Abstracts
capsules is the layer-by-layer (LbL) assembly of complementary interacting polymers
onto a colloidal template. We present here the preparation of low-fouling capsules with
tailored deconstruction properties for drug delivery. The capsules were assembled via the
LbL assembly of poly(N-vinyl pyrrolidone)Alkyne (PVPONAlk) and poly(methacrilic acid)
(PMA) by hydrogen bonding onto sacrificial silica templates. Alkyne moieties were used
to cross-link the multilayer with a degradable bisazide functional molecule through click
chemistry, resulting in capsules composed primarily of PVPON.
The PVPON multilayers are low-fouling in the presence of a number of fluorescentlylabeled proteins and the resulting capsules showed no effect on the proliferation of cells
by MTT assay. Cells incubated with various concentrations of capsules showed minimal
change in proliferation as compared with untreated samples, thereby highlighting the
biocompatiblility of the capsules. Additionally, capsules stabilized with a linker
containing a disulfide group (which is capable of being cleaved under reducing
conditions) are shown to deconstruct in the presence of 5 mM glutathione. The lowfouling properties of these capsules render them attractive materials for bioreactors,
biomarkers or drug delivery.
NANO SPRAY DRYER –SUBMICRON PARTICLES OF MINIMAL
POWDER QUANTITIES AT HIGH YIELDS
Cordin Arpagaus, Business Area Spray Drying, Büchi Labortechnik AG,
Meierseggstrasse 40, 9230 Flawil, Switzerland, [email protected]
16
Spray drying is recognized as one of the few industrial drying processes that produce
powders directly from liquid feed formulations in an operation that is continuous, easy to
control, economical, environmentally friendly and safe. It is widely used in the
pharmaceutical, biotech, food & feed, chemical and material industries. Today, there is a
high research activity in the preparation of spray dried nanoparticulate materials for novel
drug delivery systems (e.g. inhalable drugs in the form of nanocapsules, -suspensions or emulsions). A new spray dryer is described that features a unique vibrating mesh spray
generation (Fig. 1) for fine droplets (Fig. 2). A unique heater technology based on porous
metal foam provides a laminar gas flow and guarantees shortest heat up times of the
drying gas for very gentle drying condition of heat-sensitive materials. The fine spray
dried particles are separated by a novel electrostatic particle collector - a new technology
in laboratory scale – for highest particle recovery rates of any kind of material. This new
technology is particularly useful where the newest application trends focus on effective
formulation of complex and valuable drugs (highly active pharmaceutical ingredients)
and nanoparticles.
 Produce submicron- or even nanoparticles with very narrow size distribution for
new breakthroughs in R&D
 Invest only a minimal sample amount of high valuable product to receive a dry
powder
 Profit from minimal loss of high valuable products due to uniquely high yields
 Safe process time thanks to simple assembling, easy cleaning and fast product
switch
33
Abstracts
Figure 1
Figure 2
EVALUATION OF ITRACONAZOLE ENTRAPPED IN NANOSPHERES
OF PLGA FOR THE TREATMENT OF PARACOCCIDIOIDES
BRASILIENSIS
Elaine P. Cunha-Azevedo, 1; Jaqueline R. Silva1; Marigilson P. SiqueiraMoura2, Anamélia L. Bocca1; Antonio C. Tedesco2; Ricardo B. Azevedo1;
1 Laboratório de Morfologia e Morfogênese, Departamento de Genética e
Morfologia, Universidade de Brasília. 2 Laboratório de Fotobiologia e
Fotomedicina, Departamento de Química, Faculdade de Filosofia, Ciências e
Letras de Ribeirão Preto, Universidade de São Paulo. Universidade de
Brasília, Campus Darcy Ribeiro, Asa Norte, Brasília, Distrito Federal, 70910900 Brasil; e-mail contact: [email protected]
17
The Paracoccidioidomycosis (PCM) is an endemic disease of relevance in Latin
America. The current therapy for PCM falls mainly into two classes of antifungals, the
triazoles and polienos, such as itraconazole and amphotericin B, respectively. These
treatments result in serious side effects for the patients. Various strategies are set to avoid
or minimize side effects, and the drug delivery system is one option, promoting a gradual
release of the drugs. In this study, an Itraconazole nanoencapsulated technology is
applied to the treatment of PCM. The in vitro citotoxicity of hepatocytes and mesangial
cells, and antifungical activity, as well as the effectiveness in mice BALB-C infected
with Paracoccidiodes brasiliensis of Itraconazole entrapped in nanospheres were
evaluated. The citotoxicity was determined by the tetrazolium reduction, MTT assay,
after incubation for 24 hours of mesangiais cells and hepatocytes with samples tests
(ITZ-NANO- 3 and 6 mg/kg or drug free (ITZ)-50 and 100 mg/kg). The in vitro efficacy
of ITZ-NANO to PB was examined and evaluated by minimal inhibitory concentration
(MIC) and colony forming units (CFU). For the in vivo studies we did histological
examination of the lung of animals infected with 3x107 cells/ml isolated from the fungi
Pb18, and treated with either ITZ-NANO- 3 mg/kg or ITZ-50 mg/kg.
The concentrations of ITZ-NANO tested in the mesangiais cells and hepatocytes showed
34
Abstracts
lower cytotoxicity when compared with ITZ in the same concentration (3 and 6 mg/kg)
and also when we used a higher concentration (50 and 100 mg/kg) ( Figure 1). For
fungistatic activity against PB, there was no difference for the MIC of cells tretated with
ITZ NANOor ITZ. The histopathologic analysis was used to observe the formation of
granulomas and the presence of fungal cells in the animals after the treatments. In the
group without treatment, both 30 and 60 days, it was observed inflammatory infiltrations,
thick lung parenchyma and presence of granuloma and fungal cells. Histological
evaluations by using hematoxylin-eosin (HE) showed that the group treated with ITZNANO and ITZ showed reduction of inflammatory infiltrate. In the group of animals
treated with ITZ-NANO, it was not observed granuloma and also no presence of fungal
cells, which was present in lung sections from animals treated with the ITZ (Figure 2).
Our results suggest that ITZ-NANO can be a better substitute for the ITZ, since have
good efficacy against PB fungi, without side effects apparent.
HIERACHICALLY NANOSTRUCTURED PARTICLES AS A
NANOREACTOR FOR SYNTHESIS OF CORE-SHELL PARTICLES
Won San Choi¹, Hye Young Koo², Hye Min Yang¹,³, Ha-Jin Lee¹, Young
Boo Lee¹, Tae Sung Bae¹, and Il Cheol Jeon³; ¹Jeonju Center, Korea Basic
Science Institute (KBSI), 664-14 Dukjin dong 1-ga, Dukjin-gu, Jeonju, 561756, Korea; ²Korea Institute of Science and Technology (KIST) Jeonbuk 8649, Dunsan-ri, Bongdong-eup, Wanju-gun, Jeollabuk-do, 565-902, Korea;
³Department of Chemistry, Jeonbuk National University, 664-14 Dukjin dong
1-ga, Dukjin-gu Jeonju, 561-756, Korea; [email protected]
18
Hierarchically nanostructured materials having two or more levels of structure have
shown unique properties that could not be shown in their bulk counterparts. Their
importance has grown by the vast potential applications including chemical reactor,
chemical sensor, catalyst, battery, drug carrier, and encapsulation. For this reason, many
35
Abstracts
efforts have been devoted to the syntheses and developments of the novel hierarchically
structured materials. Herein we report the fabrication method for the extraordinary
spherical core-in-shell structures. Our core-in-shell particles were prepared by successive
coating of colloidal particles with various kinds of charged materials, and subsequent
calcination of the coated colloidal particles. The size of the overall shell and the core
could be controlled by using the number of coating. As-prepared, the core-in-shell
structures showed excellent ability to prepare core-shell particles composed of a wide
variety of materials. Furthermore, we expect that this approach might also be used as a
direct method for preparing hierarchical nanoparticles with tailored properties showing
individual properties from each other within the single shell.
QUANTIFICATION OF THE ENCAPSULATION EFFICIENCY IN
SINGLE SMALL UNILAMELLAR VESICLES AND INVESTIGATION
OF VESICLE-DNA INTERACTIONS
Brian Lohse, Pierre-Yves Bolinger, Andreas L. Christensen, Dimitrios
Stamou; Bio- Nanotechnology Laboratory, Department of Neuroscience and
Pharmacology & Nano-Science Center, University of Copenhagen,
Universitetsparken 5, 2100 Copenhagen, Denmark; [email protected];
[email protected]
19
Encapsulation of water soluble compounds in lipid vesicles is a central problem in the
formulation of vesicle based drug delivery vectors but it is also a fundamental step in the
use of vesicles as miniaturized bioreactors and for the building of artificial protocells.
We report a quantitative study of the encapsulation efficiency (EE) of various water
soluble fluorescent markers in single vesicles. Encapsulation efficiency was measured by
single vesicle fluorescence microscopy. The single vesicle approach revealed pronounced
heterogeneities in EE that were previously hidden due to ensemble averaging. Of
particular interest was the observation of an inverse relation between EE and vesicle
diameter. Furthermore, we report preliminary work on vesicle encapsulation of DNA and
adsorption of DNA to the vesicle membrane. As demonstrated here, single particle
analysis is essential for obtaining a detailed picture of the encapsulation process in
nanoscale containers.
SINGLE VESICLE ENCAPSULATION AND FUSION: THE DESIGN OF
AN ATTOFLUIDIC BIOCHIP
Sune M. Christensen, Brian Lohse, Pierre-Yves Bolinger, Nikos S. Hatzakis,
Michael W. Mortensen and Dimitrios Stamou, Bio–Nanotechnology
Laboratory, Department of Neuroscience and Pharmacology & Nano–Science
Center, University of Copenhagen, Universitetsparken 5, 2100 Copenhagen,
Denmark; [email protected]
20
Self-assembled nanocontainers in the form of small unilamellar lipid vesicles (SUVs)
have gathered broad interest due to their applications as intelligent drug carriers, as
biophysical model membrane systems and as ultra-miniaturised biochemical reaction
36
Abstracts
vessels. We investigate single vesicles by arraying intact SUVs on solid supports and
probing their properties by fluorescence microscopy techniques, fig. 1a. Here we adopt
this single vesicle platform to quantitatively study encapsulation efficiency (EE) of water
soluble compounds in SUVs fabricated by standard preparation techniques. The analysis
was performed by single particle colocalisation of fluorescence signals of a membrane
label and various water soluble probes, fig. 1b. Optimisation of EE is a central problem in
all applications of vesicles, especially in the formulation of drug delivery systems.
Therefore detailed knowledge of EE is of utmost importance. Our single SUV study
revealed two important aspects of EE that was previously hidden due to ensemble
averaging: (i) the presence of empty vesicles within SUV preparations and (ii) an inverse
relation between EE and vesicle diameter. Furthermore, we demonstrate how biochemical
reactions can be conducted inside single SUV containers by mixing aliquots of
encapsulated species upon SUV fusion, fig. 1c. We encapsulated the enzyme alkaline
phosphatase in one population of SUVs and immobilised them on the surface. In a
subsequent step we triggered mixing of the confined enzyme and a substrate (fluoresceine
diphosphate) by programmed fusion of the surface coupled vesicles to vesicles in
solution. Fusion caused mixing of enzyme and substrate leading to the formation of
fluorescent product (fluorescein) within the confined lumen of the surface tethered SUVs.
The mixing process was followed by three-channel fluorescence microscopy. We
monitored leakage free contents mixing of single SUV pairs that each had a volume on
the order of 1 attolitre (10-18 l). Consecuently, we have realised a soft matter based
attofluidic system that can be used to quantitatively mix biomolecular species. This
systems downscales present state of the art in miniaturisation of fluidic solutions by four
orders of magnitude.
Figure 1
37
Abstracts
APPLICATION OF POLYELECTROLYTE CAPSULES IN THE DOMAIN
OF TISSUE-ENGINEERING AS CARRIERS FOR GROWTH FACTOR
DELIVERY
Liesbeth J. De Cock,1 Bruno G. De Geest,1 Stefaan De Koker,2 Sandra Van
Vlierberghe,3 Peter Dubruel,3 Filip De Vos,4 Chris Vervaet,1 Jean Paul
Remon,1; [email protected]
1
Laboratory of Pharmaceutical Technology, Department of Pharmaceutics,
Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium;
[email protected]
2
Department of Molecular Biomedical Research, Ghent University,
Technologiepark Zwijnaarde 927, 9052 Zwijnaarde, Belgium
3
Polymer Chemistry and Biomaterials Research Group, Ghent University,
Krijgslaan 281, Building S4 Bis, 9000 Ghent, Belgium
4
Laboratory of Radiopharmacy, Department of Pharmaceutical analysis,
Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium
21
The fundamentals of tissue-engineering involve cells, scaffolds and growth factors. Cells
synthesize matrices of new tissue, while scaffolds are used as an extracellular matrix. The
function of growth factors is to facilitate and promote regeneration of new tissue by cells.
A critical point in tissue-engineering is the delivery of growth factors to the site of action.
In this project we evaluated the use of polyelectrolyte microcapsules as growth factor
carriers, incorporated within synthetic tissue engineering scaffolds. In a first step the
possibility to incorporate polyelectrolyte capsules within a synthetic scaffold was
evaluated. Therefore, calcium carbonate microparticles (CaCO3) were used as sacrificial
templates and coated with 2 bilayers of heparin and poly-L-arginine via the layer-bylayer technique. Subsequently the capsules were added to a solution of methacrylated
gelatin, followed by a freezing and thawing cycle to form a porous cryogel. Irradiation of
the cryogel with UV light resulted in crosslinking of the methacrylated gelatin. Scanning
electron microscopy on whole cryogels and confocal microscopy on sections revealed the
successful incorporation of capsules within the cryogel. In a second step it was evaluated
whether polyelectrolyte capsules could be loaded with basic fibroblast growth factor
(bFGF), a growth factor stimulating proliferation of human dermal fibroblasts. Hollow
microcapsules were obtained by the addition of an aqueous disodium
ethylenediaminetetraacetate (Na2EDTA) solution to the capsules. Hollow capsules,
coated with heparin and poly-L-arginine were loaded with bFGF through electrostatic
interaction at slightly acidic pH and low ionic strength, yielding a loading efficiency of
50 %. Upon incubation at physiological pH and ionic strength the growth factor was
released in a sustained way over a 7 day period and the amount of released growth factor
in the surrounding medium could be controlled by varying the amount of polyelectrolyte
capsules. The biological activity of the released bFGF was assessed by adding the bFGF
loaded capsules to in vitro cultured human dermal fibroblasts, followed by the evaluation
of the cell proliferation at different time points. Compared to fibroblasts incubated with
cell medium without growth factor, the cell proliferation was significantly enhanced
when bFGF was continuously released from polyelectrolyte capsules. In conclusions, we
have demonstrated that polyelectrolyte microcapsules can be efficiently incorporated
within a cryogel scaffold. Further we showed that bFGF can be encapsulated and released
38
Abstracts
from the microcapsules, resulting in an increased cell proliferation of human dermal
fibroblasts.
UPTAKE OF COLLOIDAL POLYELECTROLYTE MULTILAYER
CAPSULES BY LIVING CELLS
Loretta L. del Mercato1, Pilar Rivera Gil1 , Almudena Muñoz-Javier1,2,
Pablo del Pino1,2, Oliver Kreft3, Maximilian Semmling1,4, Susanne Kempter2,
Andre G. Skirtach3, Oliver T. Bruns5, Matthieu F. Bédard3, Joahim Rädler2, J.
Käs4, Christian Plank2, Gleb Sukhorukov3, Wolfgang J. Parak1,2
1 Fachbereich Physik, Philipps Universität Marburg, Marburg, Germany;
[email protected]
2 Universität München, Germany
3 Max-Plank-Institut für Kolloid- und Grenzflächenforschung, Golm,
Germany
4 Universität Leipzig, Leipzig, Germany
5 Eppendorf Klinikum, Hamburg, Germany
22
Uptake and processing of capsules or particles by cells are important issues with regard to
the transport of active agents into the cytoplasm. A recently introduced delivery concept
of layer-by-layer assembly of thin planar films or spherical geometries of polyelectrolyte
multilayer capsules has emerged as a universal carrier system in which cargo and
additional functionalities can be introduced as well in the cavities and in the walls of the
capsules. Polyelectrolyte multilayer microcapsules functionalized with nanoparticles are
ingested spontaneously by cells. Several studies concerning the cellular internalization
mechanism of capsules suggest phagosomal/endosomal/lysosomal perinuclear
compartments as final locations of the capsules. Although strictly speaking the detailed
uptake process of polyelectrolyte capsules by cells remains to be clarified in future
studies, some important parameters that regulate this process were elucidated in this
work. Polyelectrolyte microcapsules are deformed upon the incorporation process due to
the mechanical stress caused in the intracellular space. Deformation was dependent on
the structure of the capsule walls. Despite deformation, capsules do not lose their cargo
even upon compression inside cells. Regarding the intracellular fate of the capsules, any
colocalization with intracellular structures like endosomes or lysosomes was observed.
Thus, the results suggest that internalized capsules are trapped in acidic vesicles rather
than free in the cytosol.
USE OF DROP-ON-DEMAND NOZZLE FOR MICROPARTICLE
PRODUCTION
Jiri Dohnal and Frantisek Stepanek, Chemical robotics laboratory, ITCPrague, Technicka 5 Prague 16628, Czech Republic; [email protected]
23
One of the key issues of microparticle preparation is the control of particle size
distribution. Microparticle preparation by the “wet” technique normally involves
mechanical dispersion of two liquid phases and consequently the creation of an emulsion
39
Abstracts
by fast stirring. Microparticles prepared using stirring usually have a relatively wide size
distribution and the process is difficult to scale up. Our objective is to synthesise
microparticles that can be used in controlled release applications for which well defined
properties are a key issue. In this work we will present a microparticle fabrication
technique based on the use of a Drop-On-Deman print head. This technology can
generate small drops with uniform diameter and substitute imperfect mechanical
dispersion by stirring. The use of this technology will allow us to produce microparticles
with well defined size, morphology and porosity. We have demonstrated that the DOD
device can produce uniform droplets in the range of 20 to 60 micrometers (depending on
the parameter setting). The resulting microparticle size is then directly proportional to the
droplet size and concentration of encapsulating agent. We willl demonstrate the
microcapsule preparation on the system Gelatine – Arabic gum since it is widely used by
both pharmaceutical and food industry for coacervation of active substances.
FLUORESCENT RATIOMETRIC pH-NANOSENSORS FOR
BIODIAGNOSIS APPLICATIONS
Tristan Doussineau, Sabine Trupp, Gerhard J. Mohr, Institute of Physical
Chemistry, Friedrich Schiller University of Jena, Lessingstrasse 10 D-07743
Jena, Germany; [email protected]
24
Fluorescent sensors designed in the shape of nanoscaled objects appear as a very
promising alternative to the conventional fluorescent probes, i.e. molecular fluorophores,
in order to investigate in a non-invasive manner living cells, tissues and microorganisms.
Indeed, enhanced brightness and photostability are usually obtained and undesirable
cross-reactivity or interferences of the transduction signal prevented. Furthermore, the
possibility to tailor the composition and the architecture of these nanosensors enables the
concomitant addition of supplementary functions to the nanosensors that foster targeting
or drug delivery.
A way to design efficient nanosensors is first to embed the indicator dye in polymer
nanoparticles. As a consequence, the indicator dye does not interact directly with the
biosample reducing the toxicity and preventing cross-reactivity with proteins.
Additionally, it is possible to embed together with the indicator dye a reference dye thus
giving reliable ratiometric measurements for continuous analyte monitoring in
biosamples.
In this communication, results on the design of pH-nanosensors with core-shell
architecture will be presented. The first system consists of zeolite beta cores embedding a
flavone dye as a reference and a silica shell containing the pH-sensitive fluorescein. A
second system will be described consisting of amorphous silica cores containing a
rhodamine dye and immobilized pH-sensitive naphthalimide derivatives in the shell.
Morphological and optical properties will be shown. Both types of nanosensors exhibit a
pKa suitable for bioanalytical investigations.
40
Abstracts
INTERFACIAL RHEOLOGY OF SURFACE-ACTIVE BIOPOLYMERS:
GUM ARABIC VS. HYDROPHOBICALLY MODIFIED STARCH
Philipp Erni1, Alan Parker1 and Peter Fischer 2
1
Firmenich SA, Corporate Research Division, CH-1217 Meyrin 2, Geneva,
Switzerland; 2Institute of Food Science & Nutrition, ETH Zurich, 8092
Zurich, Switzerland; email: [email protected]
25
Gum Arabic is a dried plant exudation obtained from the stems and branches of Acacia
senegal or Acacia seyal. We study the interfacial rheology of gum Arabic at air/water and
oil/water interfaces both in shear and dilatational deformations. For shear flow
experiments, we use a biconical disk interfacial rheometer. In compression/dilatational
mode, relaxation and oscillation tests are performed in a Langmuir film balance and with
a pendant drop device. The results are compared with identical experiments performed
with adsorbed layers of hydrophobically modified starch, a common substitute for Acacia
gum. In dilatational deformations, the viscoelastic response of modified starch is similar,
but slightly weaker as compared to Gum Arabic. In contrast, we found a very different
behavior in shear flow: for gum Arabic a gel or glass-like network with dominant
interfacial storage moduli and a linear viscoelastic regime limited to small shear
deformations is observed. On the other hand, the films formed by modified starch are
predominantly viscous and the shear moduli less dependent on the deformation. The
dynamic interfacial responses also imply different stabilizing mechanisms for acacia gum
and modified starch: gum arabic produces strong, viscoelastic interfacial films, whereas
modified starch acts as a more ‘traditional’ polymeric surfactant.
26
NOVEL PARAMAGNETIC MIXED MICELLES AS POTENTIAL MRI
CONTRAST AGENTS
Chiara Giannachi*, Simonetta Geninatti Crich†, Claudia Cabella*, Chiara
Francisco, Roberta Cavalli‡, Alessandro Maiocchi*; *Bracco Imaging S.p.A.,
Centro Ricerche Bracco, Bioindustry Park del Canavese, Via Ribes 5, I-10010
Colleretto Giacosa (TO); † Center for Molecular Imaging, University of
Torino, via Nizza 52, Torino 10126; ‡ Department of Drug Science and
Technology, University of Turin, Torino 10125, Italy;
[email protected]
Magnetic Resonance Imaging (MRI) is one of the most important non-invasive imaging
modalities in clinical diagnostics and preclinical research. The success of MRI is due to
the ability to image tissues with high resolutions in three dimensions, routinely down to 1
mm at clinical field strengths. However, MRI suffers from an intrinsic insensitivity with
respect to the competing imaging modalities such as Nuclear Medicine and Optical
Imaging. This limit can be overcome by using nanosized carriers that can deliver huge
payloads of imaging reporters at the targeting site. Paramagnetic micelles have often been
considered as nanosized contrast agents for MRI applications. To this end, several Gd(III)
complexes bearing lipophilic substituents have been reported. These molecules form
41
Abstracts
aggregates in which the hydrophobic portions are oriented within the cluster and the
hydrophilic moieties (containing the Gd-probe) are exposed to the solvent. These systems
mainly act as T1-relaxation agents, whose efficiency is eventually enhanced by the long
reorientational time of the supramolecular aggregate. The objective of this work is the
design and preparation of paramagnetic micelles based on B22286, a highly stable
lipophilic Gd(III) complex synthesized in our laboratories. We evaluated three different
techniques for the preparation of the mixed micelles as follows: thin layer-evaporation
method, solvent-emulsification and diffusion method and solvent injection technique. For
each method, different surfactants/co-surfactants combinations were explored obtaining
the best formulations with the solvent injection technique. With this method, we
produced stable monodispersed mixed micelles with an average size lower than 100 nm.
Interestingly the formulation of B22286 as micellar system requires the presence of a
short and symmetric alcohol acting as co-surfactant in combination with a non ionic
surfactant. All the produced micelles were characterized measuring their size,
polydispersion index and the zeta potential. For the most promising formulations the
physico-chemical characterization was also extended to their relaxometric properties. In
particular the best mixed micelles formulation shows high relaxivity values (r1 and r2) at
any magnetic field in the range of those applied in the clinical practice. Furthermore
using some relaxivity measurements we were able to demonstrate the stability of these
mixed micelles in several media. For the above reasons we believe that the new mixed
micelles formulation of B22286 has the potential to become a suitable nanoprobe for
MRI applications.
MICROENCAPSULATION OF BIOLOGICAL OBJECTS WITH
CELLULOSE SULFATE
Kay Hettrich1, Wolfgang Wagenknecht1, Bert Volkert1, Brian Salmons2,
Walter Günzburg2,3
1
Fraunhofer Institute for Applied Polymer Research (IAP), Geiselbergstr. 69,
D-14476 Potsdam-Golm, Germany, [email protected];
2
SG Austria Pte Ltd, 20 Biopolis Way 05-518 Centros, Singapore 138668;
3
Institut of Virology University of Veterinary Medicine Vienna,
Veterinärplatz 1, A-1210 Vienna, Austria
27
Cellulose sulfate have so far received rather small attention within cellulose
derivatization reactions, as compared, for example to acetylation or nitration. Although
sulfated polysaccharides like heparin or agar[-agar] with certain properties are
encountered in nature. The synthesis of cellulose sulfate can be occurred by
heterogeneous, homogeneous or quasi-homogeneous process. The transition from a twophase to a one-phase system during the reaction is understood as quasi-homogenous
process. Cellulose sulfates with defined properties can be formed applying the discussed
three different routes for synthesis. Important characteristics of cellulose sulfates
regarding their applications are solubility (e.g. in water), rheological behavior, different
interaction with low or high molecular cations, thermo reversible gel formation,
enzymatic degradability, anticoagulant and antiviral activity. Regioselectivity of
substitution within the AGU is relevant with regard to application of cellulose sulfate in
the biomedical field. A simultaneous acetylation and sulfation of cellulose with acetic
42
Abstracts
anhydride and chlorosulfuric acid lead to a substitution of cellulose in C-6-position after
saponification of the acetyl groups. For the micro-encapsulation of biological objects e.g.
living cells for clinical applications suitable sodium cellulose sulfate should be
substituted regioselectively in C6 position with a DS between 0.3 and 0.7. The use of
cell encapsulation is a concept with an enormous clinical potential for the treatment of a
wide range of diseases. The principle is to develop an artificial, semi-permeable capsule
with sufficient permeability that nutrients and oxygen can reach the cells, and appropriate
cellular products can be released into the blood stream or to adjacent tissues. At the same
time, the capsular material must be restrictive enough to exclude immune cells and
antibodies that would cause rejection and destroy the implant. The encapsulated product
can thus be viewed as a device that allows transplantation without the need for
immunosuppression. A wide range of cells and cell lines (allogeneic or xenogeneic,
primary established or genetically modified) may be enclosed within semi-permeable and
biocompatible immobilization polymer materials.
MOLECULARLY IMPRINTED NANOPARTICLE-ON-MICROSPHERE
CHIRAL CINCHONA-POLYMERS FOR THE ENANTIOSELECTIVECONTROLLED DELIVERY OF RACEMIC OMPRAZOLE
Chutima Jantarat1, Sarunyoo Songkro1, Helmut Viernstein2, Wolfgang
Lindner3 and Roongnapa Srichana1, 1The NANOTEC Center of Excellence
and Drug Delivery System Research Center, Faculty of Pharmaceutical
Sciences, Prince of Songkla University, Hatyai, Songkla Thailand 90110,
2
Institute of Pharmaceutical Technology and Biopharmacy, 3Institute of
Analytical Chemistry and Food Chemistry University of Vienna, Vienna,
Austria 1090; [email protected]
28
Molecularly imprinted polymers (MIPs) have been investigated as a convenient means of
creating three-dimensional networks with a cavity capable of memorizing the shape and
functional group position complementary to the template molecule. The ability of
imprinted polymers to bind a template molecule with high affinity lends to their
application as excipients for sustained drug delivery. The potential use of MIPs in
enantioselective-controlled delivery has been demonstrated for chiral drugs. In the
current study, the S-omeprazole molecularly imprinted polymer (MIP) nanoparticle-onmicrosphere (NOM) with chiral cinchona functional monomer anchors have been
successfully prepared, using suspension polymerization involving agitation of the
reaction mixture at high speed. The integration of the MIP-NOM into a self-assembled
porous cellulose membrane allowed a controlled distribution and availability of the
molecular recognition sites within a porous structure. The nature of the membraneincluded microparticles determined the degree of porosity whilst the adherent
nanoparticles provided an increased surface area enabling the composite membrane to be
employed efficiently for the transmembrane transport of the S-omeprazole imprinted
molecule. In this study, These newly developed MIPs have been used to design delivery
systems for the partial selectively release of omeprazole enantiomers from racemic
omeprazole, in which NOM-MIP was encapsulated within a pH-responsive polymer of
the matrix. The prepared delivery systems have been characterized in vitro release
studies. The results demonstrate that the drug delivery system containing S-omeprazole
43
Abstracts
imprinted cinchona-polymer may have the potential for maximizing efficacy while
minimizing dose frequency and toxicity.
PRODUCTION OF HOLLOW CARBON MICROPARTICLES FROM
BIOMASS RESOURCES
Katsumi Kamegawa, Masaya Kodama, Tsuyoshi Sakaki, Kinya Sakanishi, Keiko
Nishikubo, and Yoshio Adachi, National Institute of Advanced Industrial Science
and Technology, 870-1, Shuku-machi Tosu, Saga 841-0052 Japan;
[email protected]
29
Carbon black, a typical carbon nanoparticle, is manufactured by pyrolyzing heavy oil (fossil
resources) at about 1500oC. It is used mostly as a raw material for tires. Conversion of heavy
oil consumption to the use of biomass (renewable biological resources) is demanded to retard
global warming and to preserve limited fossil resources. Lignin is an abundant biomass
resources and are produced as a by-product of paper manufacturing. For the present study, we
have examined production of carbon microparticles from lignin. The preparation procedure of
carbon microparticles consists of rapid drying of a mixed solution of lignin and inorganic salts
using a spray dryer, pyrolysis of the composite particles at 700oC in nitrogen, washing of the
pyrolyzed product with water, and drying at 120oC. Four representative forms of carbon
microparticles are presented in the figure: (a) high-strength and lightweight carbon microshell
with a thick shell (size, 0.3–5 µm; bulk density, 0.3 kg/L), (b) extraordinarily lightweight
carbon microballoon with a very thin shell (0.3–5 µm, 0.01 kg/L), (c) carbon nanobead (10–
200 nm) resembling carbon black particles, and (d) hollow carbon nanoshell (3–30 nm)
incorporated mutually in a spongy carbon shell. The inorganic salts dissolving in water were
reused after selective removal of contaminants from lignins by addition of appropriate agents
and separation of resulting precipitate. Because the carbon microparticles from biomass are
lightweight materials and show high surface areas, it is expected that they will be most useful
in such applications as a reinforcing agent for rubber, a lightweight filler, activated carbon,
toner, an anti-electrostatic agent, and a battery electrode material.
44
Abstracts
POLYELECTROLYTE NANO-ASSEMBLED MICROCAPSULES FOR
BIOSENSING OF GLUCOSE IN HUMAN SWEAT
David Haložan 1,2,3, Georg M. Guebitz 4, Gleb B. Sukhorukov 5, Helmuth
Möhwald 3, Vanja Kokol 2
1*
Institute for Physical Biology, Toplarniška 19, SI-1000 Ljubljana, Slovenia;
[email protected]
2
Institute of Engineering Materials and Design, University of Maribor,
Smetanova ul. 17, SI-2000 Maribor, Slovenia; [email protected]
3
Max-Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, D14476 Potsdam/Golm, Germany
4
Department of Environmental Biotechnology, Graz University of
Technology, Petersgasse 12, A-8010 Graz, Austria
5
Department of Materials, Queen Mary University of London Mile End
Road, London, E1 4NS, United Kingdom
30
The new biocompatible and antiallergic approach to detect selected human sweat
ingredients as glucose, important for evaluation of human physiological and metabolic
conditions, was implemented by using suitable enzymes, which are able to transfer
selected sweat substrates to optically detectable submicron products. Today the glucose
determination apparatus are widely used in common life, medicine and pharmacology.
Commercially available sensors are frequently used for detection and determination of
glucose concentration in macroscopic range. Our aim was to develop and assemble a
submicrometer polyelectrolyte microcapsule sensor that would increase the lower
sensitivity for glucose and would be capable of measuring glucose concentration above
200 mM with linear response. The enzyme’s optimal substrate activity was studied in the
polyelectrolyte LbL (Layer-by-layer) assembled microcapsules for being able to
exchange analyte with outer measuring environment, i.e. human sweat. For that purpose
GOX and HRP were encapsulated and immobilised in microcapsules with suitable
enzyme substrate, o-dianisidine or guaiacol. The efficacy of encapsulated enzymes was
determined by fluorescence spectra measurements using partially labelled enzymes with
fluorescence dyes, while the glucose detection was evaluated by UV/Vis
photospectroscopy for various reaction times (0 to 11 minutes) at 35 oC and depending on
the concentration of glucose and volume of administrated sample. Diffusion of glucose
from the bulk sweat solution through semipermeable polyelectrolyte microcapsule wall
into inner microcapsule enzyme solution was taken into account. Small ions are
distributed between inner and outer solution according to well known Donnan
distribution due to their concentration and presence of big nonpermeable macroions. The
variation in pH and salt concentrations in human sweat, depending on different skin
glands secretion in specific parts of the body, was also considered. This research has
been supported by a Marie Curie Transfer of Knowledge Fellowship of the EC FP6
(contract No. MTKD-CT-2005-029540-POLYSURF) and the Slovenian Research
Agency (Grant No. Z2-9623).
45
Abstracts
SYNTHESIS AND CONTROLLED RELEASE CHARACTERISTICS OF
HOLLOW SiO2 MICROPARTICLES
Pavel Kovačík, Aleš Zadražil and František Štěpánek, Department of
Chemical Engineering, Institute of Chemical Technology Prague,
Technická 5, 166 28 Prague, Czech Republic; [email protected]
31
The aim of this work is to fabricate hard porous micro-particles based on silica (SiO2) to
create bodies of so-called chemical robots. Porous SiO2 shells or micro-skeletons are
ubiquitous in nature – in particular in mari1303853ne microorganisms (diatoms). It is
envisaged that a chemical robot will be a simple fully synthetic “unicellular organism”,
with main attributes similar to those of living organisms, such as the ability to move in its
environment, exchange matter with its surroundings or accumulate or excrete reaction
products, except reproduction and evolution. The size range of the micro-particle entities
will be in order of 10-100 µm. There are several methods how these particles can be
prepared such as self-assembly of colloidal particles to form the so-called colloidosomes
or precipitation of silica around a template. The latter method was used for creating
porous micro-particles in this work. The procedure based on the Störber method was
used for preparing hollow silica micro-particles. The hollow core was obtained by a sol –
gel process of tetraethyl orthosilicate (TEOS) in non-ionic W/O emulsion containing
kerosene, sorbitan monooleate (Span80) and water. The second way is to use microparticles as a template (sodium hydrogen carbonate, calcium carbonate, polystyrene
beads) which is subsequently removed to create hollow core. The experimental
conditions affecting the micro-particles properties (size, thickness, permeability) were
investigated in order to precisely control characteristics of the chemical robot body. We
will show that particle size can be systematically varied in the range of 10 – 100 µm and
that the shell thickness can be changed independently of the core diameter. The particle
size distribution was measured by the laser scattering method and the microstructure of
the porous particles was visualized by SEM and x-ray microtomography. The
permeability of the silica shell was characterized indirectly by measuring the
uptake/release kinetics of a model substance (vitamin B12, methylene blue) using
UV/VIS spectrophotometry. Strategies for further modification of the properties of the
porous shell (control of porosity, pore size distribution, surface properties) will be
discussed.
NANOBIOTECHNOLOGICAL POTENTIAL OF S-LAYER COATED
LIPOSOMES
1
Seta Küpcü, 2Monika Vetterlein, 1Andrea Scheberl, 1Bernhart Schuster,
2
Margit Pavelka and 1Uwe B. Sleytr
1
Department for Nanobiotechnologie, University of Natural Resources and
Applied Life Sciences, Gregor-Mendel Strasse 33, 1180 Vienna, Austria
2
Department of Cell Biology and Ultrastructure Research, Center for
Anatomy and Cell Biology, Medical University of Vienna, Schwarzspanierstr.
17, 1090 Vienna, Austria
32
46
Abstracts
Crystalline S-layer proteins occur as outermost cell envelope component in many bacteria
and archaea. Isolated S-layer subunits are composed of a single protein or glycoprotein
species with the ability to self-assemble into well defined nanolattices on planar and
spherical surfaces (e.g. glass, silica, gold, lipid layers). These properties make S-layer
protein to ideal building blocks for nanomaterials which can be used for nanopatterning
of lipid vesicles including liposomes, emulsomes and lipid-plasmid complexes which
resemble an artificial virus envelope. Beside the thermal and mechanical stabilizing
effects of the S-layer lattice on liposomes the S-layer lattice represents a surface with a
broad functionalization potential. Chemical and genetical methods are applied for
functionalization of S-layer proteins which opens new ways for creating side specific and
biocompatible surfaces for targeting and delivery systems.
Methods for recrystallizing isolated S-layer subunits from different bacteria strains on
liposomes have been established. Recrystallization conditions have been optimized for
each distinct S-layer protein in terms of ion content of the recrystallization solution and
lipid composition of the liposomes. Liposomes coated with S-layer subunits of
Lysinibacillus sphearicus CCM2177 exhibit p4 lattice symmetry with a zeta-potential
value of -26 mV whereas with S-layer subunits of Geobacillus stearothermophilus
PV72/p2 coated liposomes are exhibiting p1 lattice symmetry and a zeta-potential of 23
mV. These data demonstrate that a basic surface manipulation of liposomes can be
induced by the different physicochemical properties of various S-layer proteins.
It is a challenge to investigate the behaviour of S-layer coated liposomes with and within
eukaryotic cells. Uptake of S-layer coated liposomes is investigated by fluorescence- and
electron microscopy. For these studies the liposomes were loaded prior S-layer protein
recrystallization either with hydrophilic or lipophilic fluorescent dyes or electron dense
macromolecules were entrapped for visualizing the liposomes by electron microscopy.
Internalization of such liposomes is investigated in various human cell lines in cell
culture. The endocytic pathway of S-layer coated liposomes could be demonstrated by
fluorescent labelling of cell compartments such as early endosomes and lysosom.
Furthermore, the application of liposomes coated with fluorescent S-layer-fusion proteins
is another promising approach to study their location in cell compartments.
Thus, S-layer coated liposomes constitute very usefull tools not only for elucidating the
uptake by eukaryotic cells but also for the production of new targeting and delivery and
systems.
ELECTROHYDRODYNAMIC JETTING OF POLYMERS USING COAXIAL NOZZLES
Min Young Kim, Hwanki Ho, Chul Ho Park, SaeHyun Park, and
Jonghwi Lee; Chung-Ang University; 221, Heukseok-dong, Dongjak-gu;
Seoul, 156-756, Korea (South); [email protected]
33
Electrohydrodynamic jetting has been used to prepare fibers (electrospinning) and
particles (electrospraying). This process uses electrostatic force applied on the surface of
jetting solution to drive hydrodynamic driving force for jetting. Chitosan is difficult to
electrospin due to their lack of chain entanglement. The concentration of chitosan
solution for spinning cannot easily be increased due to its high viscosity. A concentration
above 3% became gelled, and below 2% only particles were prepared. Thus, it was
47
Abstracts
reported that fibers could not be prepared from electrospinning of chitosan in aqueous
acetic acid. Instead of pure chitosan, a mixture of chitosan and another polymer was tried
to prepare fibers for drug delivery and tissue engineering applications. In this study,
without using an extra polymer, pure chitosan fibers were prepared from electrospraying.
Electrospraying produced well dispersed chitosan nanoparticles and encapsulation
particles, and subsequent processes assembled them into fiber structures. The fiber
formation sensitively relies on various processing parameters such as type of dispersing
medium for nanoparticles, concentration of chitosan, etc. The fibers did not show any
significant stretching of chain molecules in the examination of SEM and XRD. This
processing technique can be used for the fiber formation of polymers difficult for
electrospinning.
POLYMER-DIRECTED CRYSTALLIZATION OF ATORVASTATIN
Hyemin Choi, SaeHyun Park, Min Kyung Lee, and Jonghwi Lee; ChungAng University; 221, Heukseok-dong, Dongjak-gu; Seoul, 156-756, Korea
(South); [email protected]
34
Polymer directed crystallization has been investigated to understand biomineralization
process in nature and produce organic/inorganic hybrid materials with complex
morphologies. The existence of polymer induces crystal face-selective polymer
adsorption and mesocrystal formation, resulting in unique hierarchical materials with
structural specialty and complexity, and a size range spanning from nanometers to
micrometers. Crystallization of drug compounds has been an important issue, because it
determines drug bioavailability, stability, processability, etc. However, the polymerdirected crystallization technique has seldom been applied to the crystallization of drug
compounds. Herein, the crystallization conditions for maximizing the interactions
between polymers and drugs were examined, and the effect of various polymers on the
crystallization of atorvastatin was studied. Atorvastatin/polymer mesocrystals and their
composite encapsulation particles were successfully obtained using the polymer-directed
crystallization technique. The adsorption layer of polymer and stabilized mesocrystals of
atorvastatin produced interesting properties. The results proved that the polymer-directed
crystallization technique could be useful in the pharmaceutical research and development.
MULTI-FUNCTIONAL POLY UREA FORMALDEHYDE CAPSULES
Dennis Lensen1,2, Joost Opsteen1, Margot Segers2, Dennis Vriezema1 and Jan
van Hest2; 1Encapson B.V., Toernooiveld 1, Nijmegen,
2
Organic Chemistry, Institute for Molecules and Materials, Radboud
University Nijmegen, Heyendaalseweg 135, Nijmegen;
[email protected]
35
In the last decades, several methods have been utilized to form microcapsules, which are
used as e.g. biosensors, drug delivery vehicles, nanoreactors or self healing materials.
Here we describe the formation of poly urea formaldehyde capsules via precipitation
polymerization and two applications in the field of biomedical devices: first capsules for
self healing bone cement and second, magnetic capsules for guided imaging.
48
Abstracts
DOUBLE CONTROLLED RELEASE FROM HYBRID MATERIALS
CONTAINING MICROSPHERES AND HYDROGELS
Madarieta I. Pardo, Sáez V. Martinez, Olalde B. Graells and *Garagorri N.
Gantxegi; Health Unit of INASMET-TECNALLIA. Mikeletegui Pasealekua,
2. Technological Park. 20009 San Sebastian. Spain; [email protected]. 36
The development of release systems capable of delivering drugs over extended period of
time is deemed desirable for a variety of biomedical applications. The goal of this work
was to create hybrid materials with different release profiles. For such purpose, materials
were obtained by dexamethasone loaded PLGA-Microspheres photoencapsulation in the
polymer meshwork of a poly (ethylene glycol) hydrogel. Microspheres of 30-40µm and
2-3µm in diameter were assayed alone and in combination with the hydrogel. The
microspheres showed an optimal morphology visualized by SEM and the loading amount
of dexamethasone ranged from 65-118µg/mg and 40-50µg/mg respectively.
Dexamethasone release was studied from the microspheres, hydrogels and from the
hybrid materials. The non degradable hydrogel drug release showed an initial burst
followed by a release at a significantly low amount with the 98% of the drug released in
the first three days. PLGA microspheres controlled the release at least for two months
with a final cumulative release of 85% in 57 days for the 30-40 µm particles and 90% in
15 days for the 2-3 µm particles. The embedding of the microspheres in the hydrogel
network controlled again the release which was attenuated in a 15-25% and 50% for each
type of microsphere respectively. Since their localized and more sustained release of the
drug, these hybrid materials present promising opportunities for the design of antiinflammatory drug delivering biomaterials.
MICROENCAPSULATION BY COACERVATION OF
BIODEGRADABLE POLYMER WITH THYME OIL
Isabel M. Martins, Sofia N. Rodrigues, Filomena Barreiro and Alírio E.
Rodrigues; LSRE – Laboratory of Separation and Reaction Engineering,
Department of Chemical Engineering, Faculty of Engineering of University
of Porto, Rua Dr Roberto Frias s/n, 4200-465 Porto, Portugal; [email protected]
37
Microcapsules of polylactide (PLA) were produced by coacervation to encapsulate the
antioxidant and antimicrobian agent - essential oil of Thymus Vulgaris L. (thyme oil).
Biodegradable microcapsules of polylactide have received extensive attention as delivery
systems for drug encapsulation. This type of biodegradable polymeric carriers can be
hydrolyzed in the body to form products that are easily resorbed or eliminated. The core
material, thyme oil, is an aromatic and medicinal plant of increasing economic
importance for North America, Europe and North Africa. This essential oil is used in the
flavour and food industries. As pharmaceutical, the oils thymol and carvacrol are used in
mouthwashes, soaps and creams. The thyme oil is also used in manufacture of perfumes
and cosmetics.
49
Abstracts
The objective of this work is to develop a novel coacervation process to produce
microcapsules of PLA to encapsulate thyme oil that will be used in cosmetics. PLA is
soluble in organic solvents but insoluble in water. Generally, PLA is used to encapsulate
water soluble active principles such as drugs, pesticides and dye-stuffs by coacervation,
mainly by means of microspheres production or by using double emulsion techniques
(o/w/o). However, the objective of this work is to encapsulate thyme oil, a water
insoluble active principle that needs, in a first step, the preparation of an oil-in-water
emulsion. The novelty of our process consists on dissolving PLA in dimethylformamide
(DMF) which is a good solvent for PLA but in addition has high solubility in water.
Upon contact with water, the homogeneous solution of PLA in DMF, promotes the
precipitation of PLA around the thyme oil core. With this work we demonstrate a new,
easy and executable method of coacervation by introducing modifications on
microencapsulation process that allow the encapsulation of an oily active principle by
simply preparing an o/w emulsion. Control of size and wall thickness of microcapsules,
encapsulation efficiency, the influence of surfactants and release of thyme oil were
studied. The produced microcapsules have bimodal particle size distributions in volume
with a mean particle size of 40 µm. Microcapsules analysis by microscopy have
confirmed the spherical shape, the rough surface, and allowed the estimation of the wall
thickness around 5 µm. Quantification of the encapsulated thyme oil was performed by
gas chromatography and allowed to evaluate the quality of the encapsulated oil and
pointed out for a preferential encapsulation of thyme oil apolar compounds.
Poster Session 1 – Contributed Paper #
MAGNETIC NANOPARTICLES FOR GENE DELIVERY: SOME
DETERMINANTS OF EFFICIENT DELIVERY VECTORS
Olga Mykhaylyk, Yolanda Sanchez-Antequera, Nittaya Tresilwised, Elena
Oranskaya, Anna Slawska-Waniewska, Stefan Thalhammer, Denis Adigüzel, Markus
Döblinger, Thomas Bein, Per Sonne Holm, Zygmunt Pojda, Christian Plank.
Klinikum rechts der Isar, Institute of Experimental Oncology and Therapy Research,
Technische Universität München, Ismaninger Str. 22, 81675 Munich, Germany,
[email protected]
38
About thirty magnetic nanoparticles of the core-shell type comprising
magnetite cores of about 10 nm stabilized and decorated by selfassembly of surfactant and polymers to be suitable as components of
magnetic nucleic acids delivery vectors by magnetofection and their
formulations with nucleic acids and adeno- as well as lentiviral
particles were screened for their gene delivery efficiency in vitro. The
group of the most efficient particles was defined and characterized
with respect to their core composition, crystallite size, magnetization,
coating composition using TEM, XRD, magnetization and XPS
methods. Magnetic gene delivery formulations were optimized with
account for the association of DNAs, siRNAs and adeno- and
lentiviral particles with magnetic nanoparticles. A simple method for
evaluation of the magnetophoretic mobility and, hence, of the
magnetic moment was used to characterize the complexes and evaluate the number of magnetic
nanoparticles associated with complexe(s). Together with TEM and AFM data, these approaches
50
Abstracts
deliver information on the morphology, composition and magnetic properties of the complexes
which are important for identifying the most efficient magnetic vectors. The developed
transfection protocols can be used for cells that are difficult to transfect, such as primary cells, and
can also be applied to improve significantly viral nucleic acid delivery. With minor alterations,
these protocols can also be useful for magnetic cell labelling for cell tracking studies. Specifically,
we were interested in how physico-chemical and surface characteristics of iron oxide magnetic
nanoparticles and their complexes with adeno- and lentiviruses correlate with the infectious
potential in target cells. We have shown that magnetofection of oncolytic adenovirus does not alter
the inherent oncolytic potential of the virus but that it rather enchances virus uptake into cells.
Optimized assembling with selected magnetic nanoparticles lowers the IC50 of the adenovirus in
181RDB cells and lentivirus in umbical cord mesenchymal stem cells one order of magnitude. We
suggest a “rule” to formulate virus magnetic complexes based on our fine-tuning of the
nanoparticles-to-virus particles ratio in the range of 2.5-20 fg iron per physical virus particle
depending on the nanomaterial used. We show also that an excess of magnetic nanoparticles can
inhibit infection efficiency. The figure shows an atomic force microscopy 3D image and a contour
plot of adenovirus associated with magnetic nanoparticles. The average size of the complexes is
171±17 nm. Taking into account that rather poor information is usually available on the structure
and composition of the commercial magnetic nanomaterials, we hope that our published protocols
on synthesis of magnetic nanoparticles, their thorough characterization, formulation of the
plasmid, siRNA magnetic delivery vectors could enable further progress in the field.
INDUSTRIAL ENCAPSULATION PROCESSING
Ronald J. Veršič, Ronald T. Dodge Company, 55 Westpark Road, Dayton,
Ohio 45459-4812 USA; [email protected];
39
[email protected]
Many microencapsulation processes have been describe in the literature for over 50 years
now. But very few are in actual, large-volume, industrial practice. Examples are spray
drying, urea-formaldehyde and its many variations, and coacervation. The presenter
describes those few, chosen processes and then illustrates the reasons why they have been
selected from the innumerable candidate processes. Actual industrial products (nonpharma) are used to illustrate each process. Finally, a methodology is suggested on how
to discover and invent new processes.
LIQUID-CORE MICRO AND NANO-CAPSULES FOR THE
EXTRACTION OF DRUGS AND PESTICIDES/HERBICIDES
Ian Marison and Michael Whelehan, School of Biotechnology, Dublin City
University, Glasnevin, Dublin 9, Ireland; [email protected]
40
The presence in drinking water of commonly used medication for humans and animals
(drugs) and pesticides/herbicides used in agriculture, represents a major health hazard.
This is partly due to the techniques currently used in the water industry being unable to
efficiently remove or breakdown the compounds. Many of these compounds are
relatively poorly soluble in water and/ or have a high partition coefficient when placed in
51
Abstracts
an octanol water mixture (logP) and are therefore termed hydrophobic organic pollutants
(HOPs). As a result liquid-liquid extraction may be used to remove such compounds,
however the large quantities of the solvents required, combined with need for high power
requirements for mixing, their toxicity and difficulties in phase separation mean that this
is not a viable method. In order to address this issue, and overcome the problems with
liquid-liquid extraction, we have developed liquid-core microcapsules in which the
organic solvent is surrounded by a hydrogel membrane The vibrating nozzle technique,
using a concentric nozzle system combined with electrostatic jet break-up, was used to
produce monodisperse microcapsules with diameters below 800µm. Such microcapsules
were shown to efficiently remove a range of drugs, including carbamazepine, clofibric
acid, warfarin, diclofenac as well as a range of commonly found pesticides/herbicides,
including atrazine and 2,4-D. Interestingly, the rates and levels of removal of the
compounds was not a simple function of their logP. Consequently microcapsules were
prepared with different solvents within the cores and combined to enable complete
removal of mixtures of the compounds. The resulting microcapsules containing the HOPs
were shown to be re-usable by either back-extracting the compounds from the cores
and/or by biological breakdown using Pseudomonas sp. Preliminary experiments have
been carried out with self-assembling liquid-core nanocapsules and shown to be even
more efficient at removal of the HOPs, with extraction times of seconds compared with
minutes for the microcapsules. In a further development of this extraction technology
(capsular perstraction), the liquid-core microcapsules have been developed for use in the
pharmaceutical industry. An example is the microbial production of the antibiotic and
anti-cancer compound geldanamycin (GM). This fermentation is currently un-economic
due to product inhibition as well as the instability of GM under the production conditions.
By addition of sterile liquid-core microcapsules to the fermentation medium, the GM
could be removed at a rate faster than that of the production rate resulting in higher
production yields and long term stability.
DEGRADABLE POLYELECTROLYTE MICROCAPSULES FOR
BIOMEDICAL APPLICATIONS
Bruno G. De Geest, Stefaan De Koker, Laboratory of Pharmaceutical
Technology, Department of Pharmaceutics, Ghent University, Harelbekestraat
72, 9000 Ghent, Belgium; [email protected]
41
Polyelectrolyte capsules have emerged as novel drug delivery systems which hold
potential for the delivery of macromolecular drugs to phagocyting cells. These capsules
are fabricated by layer-by-layer coating of a sacrificial template followed by the
dissolution of the template resulting in a hollow capsule. Macromolecules can be
encapsulated within the capsules’ hollow void using a template pre-loaded template or by
post-loading by reversible switching the permeability capsules’ membrane .
The main advantages of these capsules are (1) their multifunctionality which allows to
incorporate a wide variety of species (such as e.g. synthetic polymers, proteins, nucleic
acids, lipids, nanoparticles, etc…) both in their hollow void as well as their membrane
which allows one to equip the capsules with different bio-active properties, (2) the
ability to tailor their physicochemical properties to the nanoscale by varying the capsules
size, shell thickness and shell constituents and (3) their easy of preparation under mild
52
Abstracts
all-aqueous conditions without the sue of organic solvents, reactive chemistry or high
shear forces which are often employed in traditional micro-encapsulation protocols.
Here we present degradable polyelectrolyte capsules and show their potential as antigen
delivery vehicle for antigen delivery. We assed the cellular uptake and antigen processing
and presentation by dendritic cells in vitro and went further in vivo to elucidate the
induced immune response after both subcutaneous and pulmonary delivery. We show that
by varying the capsules’ surface chemistry the type of immune response can be tailored
and finally we demonstrate protective immunity in a melanoma tumour model.
FRAGRANCE ENCAPSULATION IN MICRO AND NANOPARTICLES
Christian Quellet, Givaudan Schweiz AG, Ueberlandstrasse 138, CH-8600
Dubendorf, Switzerland; [email protected]
42
Microencapsulation has become a mature technology within the fragrance industry and
several microencapsulated products are now found in the market place, such as spray
dried powders and core-shell “scratch and sniff” aminoplast microcapsules. Alternatively,
plain (or matrix) particles offer interesting diffusion-driven release patterns, which can be
controlled by controlling the structure of the particle, the nature of the matrix materials
and the selection of the fragrance molecules to be encapsulated. In this presentation, the
major scientific and technical challenges underlying the encapsulation of fragrances in
diffusive particles are reviewed, emphasizing both thermodynamic and kinetic aspects.
The advantages and disadvantages of nano-encapsulation compared to microencapsulation are also reviewed in the specific context of matrix particles.
MANUFACTURING MICROCAPSULES FOR ADVANCED MATERIALS
Thorsten; Brandau, Egbert, Strohm, Holger; BRACE GmbH, Taunusring
50, D-63755 Alzenau, Germany; [email protected]
43
Applying vibrating nozzle processes for the production of microspheres and
microcapsules has a lot of advantages when compared to other methods: Vibrating nozzle
processes render it possible to produce particles with a monomodal grain size
distribution and a single sharp maximum. dmax/dmin-values lower than 1.10, 1.05, or
even 1.01 are customary for spherical granules produced with a vibrating nozzle
microsphere unit designed by BRACE (see Figure 1).
BRACE microspheres are solid spheres with a matrix-encapsulated active agent whereas
BRACE microcapsules consist of a solid shell and a liquid or solidified core. These two
types of microgranules differ mainly in their release profiles: Microspheres usually show
diffusion controlled release profiles with a permanent release rate that is controlled
kinetically by means of the particle size, whereas microcapsules expel their content with
a single burst as the shell breaks. On the other hand, microcapsules may exhibit
extremely slow release rates when appropriate materials are used.
Various applications have shown that microspheres produced with laminar flow breakup
53
Abstracts
processes have many advantages compared to classical preparation methods as spraydrying or spray-cooling. Due to the laminar nature of the flow, no sudden demixing
processes occur when the flow is exiting the nozzle. Since the processes lead to
monomodal size distributions, no polymorphisms occur. A truly controllable controlled
release profile can therefore be designed by manipulating only one process parameter
(particle size) instead of various ones such as load, size, drying rates etc.
By applying the double nozzle process for the production of core-shell microspheres, new
materials with exiting properties can be obtained. These "real" capsules can be designed
to release their contents with a burst as soon as the capsule becomes subject to low
pressure, or to release their contents extremely slowly over a long time. Therefore, it
becomes possible to provide solutions for both flavour chemistry and textile
applications. Since the processes are easily up-scalable, the retesting and scale-up time
from laboratory-size to production-size throughputs is short. Usually, a production unit
runs with the same feed compositions and the same parameters as the desktop unit,
making it possible to test all parameters and recipes in small scale before putting the
production unit.
Figure 1
MICROCAPSULES WITH CONTROLLED AND REMOTE RELEASE
H. Möhwald, A.G. Skirtach, D. Volodkin, D.G. Shchukin; Max-PlanckInstitute for Colloids and Interfaces, Am Mühlenberg 1, 14476 PotsdamGolm, Germany; [email protected]
44
Electrostatic, hydrogen bonding and hydrophobic forces have been used to form
polyelectrolyte multilayers and capsules with well-defined wall, diameter, and
composition of polymeric, biological, and inorganic molecules or particles. These weak
interactions can be manipulated to control properties, in special permeability and
adhesion. They exhibit glass transitions between room temperature and 90 C, depending
on composition, pH, and salt. At high temperature, the permeability is drastically
increased which may be used for environmentally dependent release. Inserting metallic
nanoparticles as strong IR absorbers also remote and local release control is achieved via
IR irradiation. This may be used for intracellular drug administration as well as for selfrepairing coatings. These capsules as well as liposomes can be incorporated into surface
coatings to obtain functional films. Two of their application perspectives will be
described: (1) Encapsulating anticorrosion agents these will be released upon local
54
Abstracts
potential changes accompanying a defect. The latter will thus be annealed and we have
thus constructed a self-repairing coating; (2) Encapsulating a drug and releasing it
triggered by light may influence cells attached to the surface.
LIPID NANOPARTICLES FOR THE DELIVERY OF ACTIVES IN
PHARMA, COSMETICS & CONSUMER CARE
Cornelia M. Keck, Department of Pharmaceutics, Biopharmaceutics &
NutriCosmetics, Free University Berlin, Kelchstr. 31, 12169 Berlin,
Germany, [email protected]
45
Despite that solid nanoparticles can improve the delivery of actives, there are no
therapeutic pharma products on the market (e.g. polymeric nanoparticles), the use in
cosmetics is limited. Reasons are e.g. lack of accepted status of excipients and of large
scale production methods. In contrast, lipid nanoparticles are made from toxicologically
accepted surfactants and lipids, large scale production is possible by high pressure
homogenization. The lipid nanoparticles followed the way of the success of the
liposomes, which were first introduced to the cosmetic market (Dior, 1986) and later to
pharma (first products around 1990). The first cosmetic products with lipid nanoparticles
appeared on the market in 2005 (Dr. Rimpler), and now almost 40 products exist
worldwide (e.g. La Prairie). Due to the solid character of the particle matrix, the lipid
nanoparticles are more stable than liposomes, protect incorporated actives against
degradation and can modulate their release. Oral bioavailability enhancement was shown
for e.g. cyclosporine, fenofibrate and testosterone undecanoate. Lipids are known to
promote the absorption of many drugs which is exploited in the lipid nanoparticles. The
first pharma development will go into clinical phase I in 2010.
ONE PROCESSING TECHNOLOGY – VARIABLE APPLICATIONS
Gülden Yılmaz, Biobased products Bussiness Unit, Agrotechnology and
Food Innovations B.V., Wageningen UR, Bornsesteeg 59 6708PD
Wageningen, The Netherlands. [email protected]
46
Especially during the past decades controlled release technology has received a
considerable attention for high volume applications. As a result, for these types of
applications, most efforts are presently focused on continuous processing technologies
and abundant matrix materials such as extrusion technology.
By applying extrusion technology, encapsulation can be (cost) effectively and efficiently
accomplished, with tailored release properties, such as extrusion technology.
Furthermore this technology also provides the possibility to modify the formulation while
performing encapsulation via enzymatic or chemical routes. A wide range of products
are made available in the form of gels, coatable liquids, large range of particle sizes and
forms as well as different release profiles and patterns are produced utilizing extrusion.
The flexibility in utilizing extrusion technology has not only made the high volume
applications available in an economically feasible manner but also opened new
application fields for a wide range of encapsulants in the areas of cosmetics, personal
55
Abstracts
care, household products, laundry applications, food, agriculture, pharmacy, biomaterials,
textile, packaging, specialty papers and polymer processing.
To conclude, encapsulation and controlled release of a wide range of compounds (solid,
liquid, volatile, heat and/or oxidation sensitive) can be achieved in an efficient and costeffective manner utilizing the extrusion technology. This is probably one of the main
reasons for the emerging acceptance of this technology in numerous application areas of
controlled release. Furthermore, the modification of the formulation characteristics can
easily be done by means of small modifications to the processing technology and the
components in the formulation.
PARTICLE ENGINEERING TO DESIGN PROTECTION AND RELEASE
OF MICROENCAPSULATED BIO-ACTIVES
Jean Antoine Meiners; MCC Micro Capsule Concepts sa, Avenue de la Gare
6a, 2013 Colombier, Switzerland; [email protected]
47
56
Abstracts
The purposes to perform micro encapsulation of bio-actives may be of different natures,
but they have a common denomination i.e. delivery and release at the targeted place. A
vast majority of these micro encapsulates require protection against moisture: moisture in
the processing phase, moisture during shelf life or protection against body fluids. The
protection may be for a short or prolonged period and moisture may be accompanied by
heat treatment.
Drying methods will have great importance for the particle shape and size. Spray drying
will generate fine particles; freeze drying will result in flake shape with a large particle
size distribution. Fluid bed drying and Zeolite drying may give particles a more spherical
shape, which allows for increased micro encapsulation efficiency.
Particle characterisation can be described by particle size, shape, internal structure and
surface properties. All these elements play an important role for the quality of the micro
encapsulation. Wall thickness may play a decisive role in efficient protection. Wall
thickness should be equal at all places surrounding the core substance. Insufficient
thickness could lead to premature leakage; too much coating may affect the release
properties in situ.
Total surface area to cover equally the core particle will be the primary characteristic to
observe. Health and regulatory limitations for the use of certain polymers will cause
restrictions in the choice of technology used for the micro encapsulation process. This
document covers a composite particles approach, geared to the engineering of a particle
with optimal physical properties for micro encapsulation purposes. Resulting capsules
will be in the micro size range.
Example particle structures:
Coating thickness as a function of particle surface area: 40 % coating
ENCAPSULATION WITH ALGINATES
Berit L. Strand, Gudmund Skjåk-Bræk. Department of Biotechnology,
Norwegian University of Science and Technology, Trondheim, Norway.
[email protected]
48
Alginates are polysaccharides found in nature as structural component in marine brown
57
Abstracts
algae and as capsular polysaccharide in some soil bacteria. Alginates are used as
immobilization material for cells providing a mild encapsulation protocol by ionic cross
linking at physiological conditions. The alginate gel capsule can serve as protection
against the host immune system upon transplantation of therapeutic cells. This may allow
treatment of different diseases, like diabetes mellitus, Parkinsons and brain tumors by cell
transplantation without the use of immune suppressive drugs. Alginates are liner
copolymers of 1-4 linked β-D-mannuronic acid (M) and α-L-guluronic acid (G). The
physical properties of alginate gels correlate with alginate composition. Blocks of G
strongly contribute to gel formation. However, recently, the role of alternating sequences
in Ca-alginate gels has been elucidated. Enzymatic modification of alginates allows
tailoring of composition and capsule properties. The lecture will focus on the use of
alginate as encapsulation material for cells, in particular pancreatic islets for the treatment
of diabetes. Important capsule properties such as stability, permeability and
biocompatibility and the dependence on alginate and capsule composition will be
covered.
Poster Session 2- Contributed Paper
PEPTIDE-MEDIATED DELIVERY OF OPTICAL NANOSENSORS INTO
S. CEREVISIAE
Lise Junker Nielsen, Veli Cengiz Ozalp and Lars Folke Olsen, Department of
Biochemisty and Molecular Biology, University of Southern Denmark,
Campusvej 55, 5230 Odense M, Denmark; [email protected]
49
In the study of the cell metabolism, knowledge of the concentration profiles of metabolites in
time and space is key to understanding the dynamics of metabolic activities in the cell. Optical
nanosenors present an interesting tool in this regard, as optical nanosensors allow real-time
monitoring of small metabolites in living cells. In order for the optical nanosensor to be truly
effective, a mode of intracellular delivery is needed, which ensures maximum loading of the
nanosensors with minimum cell pertubation. Several techniques have been employed for
nanosensor delivery, including gene gun delivery, electroporation, liposomal transfection and
recently peptide-mediated delivery. Here we present a novel mode of delivery of a pH
nanosensor into S. Cerevisiae utilizing the cell penetrating nature of cell-penetrating peptides
(CPP's). The pH nanosensor is based on a pH sensitive fluorescent dye incorporated into a
polyacrylamide nanoparticle, which was functionalized with two different CPP's known to
mediate intracellular delivery of GFP or fluorophores into S. Cerevisiae. Of these two CPP's
the artificial MAP peptide showed the best results in mediating intracellular delivery of the
nanosensor, as determined by fluorescence spectroscopy. The localization of the nanosensors
within the yeast cells was determined by confocal microscopy, and the intracellular pH of the
yeast was measured and compared to results using other intracellular pH probes. The use of
the MAP-peptide to mediate intracellular delivery can be readily extended to other
polyacrylamide-based nanosensors, and possibly also nanosensors based on other nanoparticle
formulations.
58
Abstracts
Poster Session 2- Contributed Paper
DEVELOPMENT OF NANOPARTICLES CONTAINING
PHOTOSENSITIZER WITH DIBLOCK COPOLYMER FOR
PHOTODYNAMIC THERAPY
Tsutomu Ono*, Ken Hirota*, Taro Shiraishi**, Ken-ichi Ogawara**,
Kazutaka Higaki**, and Isao Sakata†, *Division of Sustainability of
Resources, Graduate School of Environmental Science, Okayama University;
**Division of Pharmaceutical Sciences, Graduate School of Medicine,
Dentistry and Pharmaceutical Sciences, Okayama University; †Green Gold
BioSystem Inc., 3-1-1 Tsushima-naka, Okayama 700-8350, Japan;
[email protected]
50
Photodynamic therapy (PDT) requires the efficient delivery of photosensitizers to the
tumor neighbourhood. General features of tumors include leaky blood vessels and
ineffective lymphatic drainage. Therefore, nanocarriers containing hydrophobic
photosensitizers access and accumulate in the tumors though the enhanced permeability
and retention (EPR) effect. In this article, we developed biocompartible nanoparticles
containing water-insoluble porphyrin derivatives by a solvent diffusion method using
diblock copolymer. It is known that the nanoparticles with diameters <150 nm are more
useful for EPR effect. By the combination of water- and oil-soluble poly(ethyleneglycol)poly(lactic acid) (PEG-PLA) copolymers, PEG-coated PLA nanospheres with less than
100 nm in diameter were obtained. Furthermore, hydrophobic porphyrin was completely
encapsulated in the particles. Singlet oxygen was released from the porphyrinencapsulating nanoparticles by light irradiation, whereas porphyrin embedded in PEGPLA nanoparticles did not diffuse in water. In addition, we found that colon-26 tumor
cells were killed by visible light irradiation in vitro in the presence of 50 nM porphyrin
embedded in PEG-PLA nanoparticles. Since this nanoparticle was easily prepared with
only nontoxic copolymer and drug, it would be a promising nanocarrier for PDT.
APTAMER EMBEDDED POLYACRYLAMIDE NANOPARTICLES
USED AS NANOSENSORS FOR METABOLITE DETECTION IN VIVO
Veli Cengiz Ozalp, Lise Junker Nielsen and Lars Folke Olsen, Department of
Biochemistry and Molecular Biology, University of Southern Denmark,
Campusvej 55, Odense 5230, Denmark; [email protected];
51
Metabolite sensing is an important tool in understanding cell metabolism. Optical
nanosensors are especially interesting since they allow real-time monitoring of metabolite
concentrations to facilitate our understanding of the dynamics of cell metabolic activities.
We developed an optical sensor based on aptamer recognition confined in
polyacrylamide nanoparticles to measure adenosine nucleotide content inside cells.
Aptamers are biorecognition elements selected through an evolutionary procedure from a
combinatorial nucleic acid library. There has been numereous applications in sensor field
based on aptamers since the invention of the selection method. The main attraction of
aptamers as biorecognition units comes from artificial selection procedure allowing to
obtain an aptamer for any desired target. In vivo applications of aptamers reported in the
literature include targeting specific proteins in subcellular compartments for therapeutic
59
Abstracts
and research purposes and controling specific gene transcriptions. The susceptibility of
nucleic acids to nucleases and structural instability in cell environments are two major
problems encountered in such studies. Modification of nucleic acids to make them
nuclease resistant (2’-protected nucleotides like 2′-fluoro,2′-O-methyl, locked nucleic
acids; phosphothiate linkages) is the major approach to overcome limitations imposed by
enzymatic susceptibility, but also complicates the selection procedure. Nanoparticles
confinement of aptamers can be an excellent alternative to prevent enzymatic degedation
of aptamers inside cells during metabolite measurements. A pH nanosensor based on
fluorescent dyes and a phosphate nanosensor based on fluorescent protein sensor have
already been sucessfuly used for in vivo measurements showing that acrylmide particles
at nanometer scales allow rapid diffusion of small molecules into nanoparticles indicating
applicability of such designs. A fluorescent ATP switch probe based on an earlier
selected DNA aptamer was embedded in polyacrylamide nanoparticles with diameter of
28 to 35 nm. The aptamer nanoparticle sensor was characterized for specific detection of
adenosine nucleotides in buffer solutions. The reponse of the aptamer switch probe
embedded in acrylamide nanoparticles was similar to the response of the free aptamer in
solution. The enzymatic stability of nanoparticle-confined aptamers were tested by
activity experiments in the presence of DNase. Finally, synthesized aptamer nanosensors
were electroporated into yeast cells and the total concentration of adenosine nucleotide
was determined in live cells. Aptamer-based polyacrylamide nanosensors as shown here
can be readily extended to monitor any low molecular weight compound inside live cells
by selecting new aptamers, converting them into fluorescent switch probes and
embedding them in polyacrylamide nanoparticles.
ENCAPSULATION OF GOLD NANOPARTICLES IN A PNIPAM
MICROGEL: NANOREACTORS AND MOLECULAR TRAPS FOR SERS
R. Contreras-Cáceres1, S. Carregal-Romero, R. Álvarez-Puebla2, I. PastorizaSantos2, J. Pérez-Juste2, J. Pacifico2, L. M. Liz-Marzán;2(1)Depto. de Física
Aplicada, Univer. de Almería, Ctra. Sacramento, 04120, Almería, Spain, (2)
Dpto. de Química Física- Unidad Asociada CSIC-U. Vigo, 36310, Vigo,
Spain; [email protected]
52
Nanocomposite materials consisting of a colloidal metal nanoparticle within a synthetic
polymer hydrogel shell have attracted great attention due to potential applications in
several fields such as catalysis, photonics, electronics, optics and biomedicine. Within the
polymeric nanoparticles the field concerning stimuli-responsive nanomaterials has been
investigated intensively in the past years. Among then one of the most commonly studied
is the poly(N-isopropylacrylamide) (pNIPAM), that is, a thermoresponsive polymer that
undergoes a phase transition from a hydrophilic, water-swollen state to hydrophobic,
globular state when heated above its lower critical solution temperature (LCST) which is
about 31-32ºC in water.
In this work we are proposing an easy two-step procedure to pNIPAM encapsulate
cetyltrimethyl ammonium bromide (CTAB) stabilized metal nanoparticlesn; the first step
consisting of a CTAB promoted polystyrene coating of the metal nanoparticles in order
to avoid aggregation and make them fully compatible with the precipitation
60
Abstracts
polymerization of NIPAM in the second step. Figure 1 shows a representative TEM
image of the Au-pNIPAM core-shell system.
The study by UV-vis spectroscopy of the nanocomposites reveals that they present
thermoresponsive optical (see Figure 1). A closer look at the position of the surface
plasmon band of the gold nanoparticles shows that as the microgel collapses the band
red-shifts ca. 10nm. This effect should be interpreted as a consequence of a core-shell
structure since an increase in the local refractive index of the gold nanoparticles.
The thermoresponsive properties of the systems is expected to allow us to control the
catalytic properties of metal nanoparticles, as well as to control the interparticle distance
in order to obtained two dimensional arrays. Recently, we have shown its applicability as
molecular traps for surface-enhanced, spectroscopic, ultra-sensitive analysis.
53
BIOFERROFLUIDS FROM MAGNETIC POLYMER
NANOCOMPOSITES
A. Millán1, R. Piñol1, N.J.O. Silva1, L. Gabilondo1, G. Ibarz1, L. Mohamed1,
V. Sorribas2, R. Villa-Bellosta2, M. Gutiérrez3, M.S. Romero3, J.A. Moreno3,
F. Palacio1; 1Instituto de Ciencia de Materiales de Aragón, CSIC – University
of Zaragoza, 50009 Zaragoza, Spain; [email protected]; 2Department of
Toxicology, University of Zaragoza, 50009 Zaragoza, Spain; 3Department of
Hematology, University of Zaragoza, 50009 Zaragoza, Spain.
In this contribution the preparation of highly stable and persistent dispersions of
superparamagnetic maghemite nanoparticles in a biocompatible fluid is described. The
interest of maghemite nanoparticles extends into many areas of science and technology.
They are particularly attractive for biomedicine where they are used as contrast agent in
magnetic resonance imaging, drug targeting, immunoassays, molecular biology, DNA
purification, cell separation and purification and hyperthermia therapy. The magnetic
properties of maghemite nanoparticles change with size, internal structural disorder,
aggregation, and interparticle separation. Therefore, to establish structure/properties
relations and then suitable applications, a preparation methodology where these factors
can be varied independently while keeping a narrow size distribution is very necessary. A
nanocomposite made of maghemite nanoparticles uniformly distributed in a polymeric
matrix can be prepared as a previous step to the particles dispersion in a fluid. Although
nanocomposites have been produced from a large variety of polymers they often show a
wide nanoparticles size distribution and they do not permit the variation of particle size in
a large range. Here, we describe a method for the preparation of maghemite polymer
nanocomposites with an average particle size varying regularly from 1.5 to 16 nm. The
method is based on the use of N-base polymers that can form coordination bonds with
transition metal ions. Maghemite is produced by in situ hydrolysis of iron halogen salts
within a poly(4-vinylpyridine) (P4VP) polymer. The iron oxide nanoparticles are isolated
and uniformly distributed within the matrix. Size distribution was determined by XRD,
TEM and SAXS. Particle sizes are well controlled with 15% of size dispersion, not far
from that obtained in organic solvent methods. Maghemite crystalline phase purity has
been established by X-ray diffraction, TEM and Fe Mössbauer spectroscopy. The
61
Abstracts
nanocomposite is dissolved and the resulting nanoparticles are further coated with
hydrophilic and biocompatible polyethilenglycol (PEG) to make them persistent in the
blood stream. The encapsulated maghemite nanoparticles formed a colloidal suspension
in phosphate buffer saline solution (PBS) at physiological pH=7.4 obtaining a
biologically compatible ferrofluid. Size distribution of nanoparticles in the ferrofluid is
determined by Dinamic Light Scattering (DLS). In vitro and in vivo toxicology results
and in vitro hematology tests for the behaviour of the ferrofluid in blood are also
presented.
SMECTIC POLYMER VESICLES
Lin Jia1, Rafael Piñol1, Amin Cao2, Patrick Keller1, Xiangjun Xing3, Mark
Bowick3,Daniel Lévy1, Min-Hui Li1.
1
Institut Curie, CNRS, Université Pierre et Marie Curie, Laboratoire
Physico-Chimie Curie, UMR168, 26 rue d’Ulm, 75248 Paris CEDEX 05,
France, [email protected]; 2 Laboratory for Polymer Materials, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin
Road, Shanghai 200032, China; 3 Physics Department, Syracuse University,
Syracuse NY 13244-1130, USA
54
Polymer vesicles are stable and robust vesicles made of block copolymer amphiphiles.
Recent progress in the chemical design of block copolymers opens up the exciting
possibility of creating a wide variety of polymer vesicles with different fine structures,
functionalities and geometries. Polymer vesicles not only constitute useful systems for
drug delivery or micro/nano-reactors but also provide valuable models for exploring the
physics of two-dimensional order in curved spaces. By choosing suitable liquidcrystalline polymers for one of the copolymer components one can create vesicles with
additional order in the two-dimensional membrane itself. Here we report ellipsoidal
smectic polymer vesicles and faceted smectic polymer vesicles, formed from amphiphilic
block copolymers in which the hydrophobic block is a smectic liquid crystal polymer.
Smectic order on shapes of spherical topology inevitably possesses topological defects
(disclinations). The competition between liquid crystal frank energy and membrane
bending energy associated with the topological defects are responsible for the ellipsoidal
shape and faceted shape observed in two kinds of polymer vesicles with smectic order in
the membrane. These smectic polymer vesicles offer novel examples of the interplay
between orientational/positional order and the curved geometry of a two-dimensional
membrane.
HYBRID NANOSTRUCTURED MICROCAPSULES COMPOSED OF
SILICA NANOPARTICLES AND LIPID EMULSIONS:
ENCAPSULATION AND DELIVERY OF POORLY SOLUBLE DRUGS
Angel Tan1,2, Spomenka Simovic1, Andrew Davey2, Thomas Rades3 and
Clive A. Prestidge1; 1Ian Wark Research Institute, University of South
Australia, 2Sansom Institute, University of South Australia, 3University of
Otago, New Zealand; [email protected]
55
62
Abstracts
We report on a new encapsulation and delivery vehicle for lipophilic molecules based on
controlled assembly of sub-micron lipid emulsions and silica nanoparticles into dry
microcapsules with an internal nano-porous structure (see Fig. 1). The specific internal
matrix structure of the capsules (i.e. oil, emulsifier and drug embedded in a
nanostructured silica matrix) facilitates increased drug loading compared with
conventional lipid carriers, enhanced solid state stability, redisperability from the dry
state, enhanced in vitro drug dissolution kinetics and improved orally dosed
pharmacokinetics (in vivo studies in rat model) in comparison with positive control
formulations and commercial products. Case studies are presented for poorly-water
soluble, non-steroidal anti-inflammatory drugs (NSAIDs). The mechanisms of action for
this nanostructured hybrid delivery system have been explored and are discussed. These
hybrid lipid-silica (LipoceramicTM) microcapsules have wide ranging applications, e.g.
as pharmaceutical, cosmetic and food products.
Figure 1. SEM images of hybrid lipid-silica (LipoceramicTM) microcapsules.
DELIVERY OF MICROCONTAINERS WITH ACTIVE COMPONENTS
TO CELLS
Pilar Rivera Gil1, Bruno G. De Geest2 and Wolfgang J. Parak1
1
Biophotonic, Department of Physics, Philipps Universität Marburg,
Germany; [email protected];
2
Laboratory of Pharmaceutical Technology, Department of Pharmaceutics,
Ghent University, Belgium
56
Polyelectrolyte capsules are made by layer-by-layer assembly of oppositely charged
polyelectrolytes onto a template, which is at the end of the synthesis dissolved to obtain
hollow capsules. These capsules can be filled with different bioactive molecules like
drugs, antigens or genetic material for different purposes such as disease treatment,
vaccination or gene delivery. For example, capsules filled with a pH-sensitive dye are
taken up by cells and are able to deliver information about the local concentration of
protons inside the cells. Using biological charged materials such as dextran and Larginine, biocompatible and biodegradable hollow capsules are synthesized. By
encapsulation of DQTM-Ovalbumine, a fluorogenic substrate for proteases the degradation
of the capsules can be spectroscopically controlled. Furthermore, upon capsule
63
Abstracts
biodegradation the encapsulated protein is available for enzymatic digestion. In this
work, the intracellular processing of proteins mediated by biodegradable capsules is
achieved.
SYNTHESIS OF POLYURETHANE-UREA MICROCPASULES WITH
PERFUME FOR TEXTILE APPLICATION
Sofia N. Rodrigues, Isabel M. Martins, Filomena Barreiro, Vera Mata and
Alírio E. Rodrigues, LSRE – Laboratory of Separation and Reaction
Engineering, Department of Chemical Engineering, Faculty of Engineering of
University of Porto, Rua Dr Roberto Frias s/n, 4200-465 Porto, Portugal;
[email protected]
57
This work is a contribution to the introduction of emergent technologies in the textile
sector, namely the microencapsulation of fragrances and its application to obtain addedvalue products. Polyurethane/urea (PUU) microcapsules with a perfume have been
produced using the interfacial polymerization technology for industrial application on
textile substrate having in view man suits production.
The majority of the available commercial microencapsulated fragrance systems for textile
applications are based on formaldehyde systems (phenol-formaldehyde or melamineformaldehyde resins), which are facing under the present environmental policies, several
restrictions. In such context, the production of PUU microcapsules using the interfacial
polymerization technology was performed as these systems appear as more attractive
environmental friendly solution. Moreover, they are known as versatile polymer systems
which can be tailor-made from a wide range of raw materials in order achieve the desired
physical chemical and mechanical properties. The only drawback is that PUU systems
must be designed and optimized taking into consideration the particularities of the active
principle to be encapsulated. The extent of reaction of PUU microcapsules formation was
followed by Fourier Transform Infrared Spectroscopy. Size distribution and morphology
of the produced microcapsules were studied using particle size analysis, optical
microscopy and scanning electron microscopy. The microcapsules mean size (based on
volume distribution) of produced microcapsules is 10 µm and thickness around 1µm.
Impregnation on textile substrates was tested both at laboratory level and at industrial
scale. The fragrance release from textile substrates was measured with headspace
chromatography. The content of microcapsules was released with light abrasion to
simulate day-to-day wear, and fabrics impregnated at laboratory scale have survived to
9000 abrasion cycles. Microcapsules have continued to release aroma up to 5 dry
cleaning washing cycles. The encapsulation efficiency and the presence of perfume on
textile substrate were quantified through GC-FID-Headspace analysis. The encapsulation
efficiency accounts for 55% of the loaded perfume used in the encapsulation process.
Comparing each component of the perfume with their odor threshold the results showed
that musk and limonene scent odor values are the highest so these are the components
that we smell more. The amount of limonene component in the fabric was compared with
its threshold and the odor value was calculated confirming that there is a decrease on
odor value with 5 dry cleaning cycles.
64
Abstracts
CONTROLLED RELEASE STUDIES OF DEXAMETHASONE FROM
NANOMETRIC HYDROGELS FOR OPHTHALMIC APPLICATIONS
Virginia Sáez-Martínez, Nerea Argarate, Nerea Garagorri; InasmetTecnalia, CIBER of Bioengineering, Biomaterials and Nanomedicine, Paseo
Mikeletegui 2, 20011, Donostia-San Sebastian, Spain; [email protected]
58
Surgery and material implantation involve inflammation processes. For this reason it is
important to deliver an antiinflammatory drug locally and over an extended period of
time. On the other side, most antiinflamatory drugs have limitations in clinical
administration due to their poor solubility and other unfavourable properties. The goal of
this work is to develop an easy technique to manufacture nanometric polymeric hydrogels
for clinical administration of antiinflamatory drugs with best efficacy and least side
effects. These nanogels can show a very fast swelling-deswelling properties and can
respond to changes in the surrounding conditions. Dexamethasone was chosen as a
prototypical antiinflamatory drug. Nanogels of N-Isopropopylacrylamide-co-acrylic acid
were prepared by precipitation polymerization in water. Several parameters were studied
to improve the encapsulation efficiency of the nanogels and the quality of the in vitro
drug release.
PHOTOPOLYMERIZATION OF FULLERENES ENCLOSED IN SWNT
Yuika Saito, Mitsuhiro Honda, Prabhat Verma and Satoshi Kawata,
Department of Applied Physics, Osaka University, 2-1 Yamadaoka, Suita,
Osaka, Japan 565-0871; [email protected]
59
The photopolymerization of fullerene C60s encapsulated inside single-walled carbon
nanotube (SWNT) is investigated in comparison with the non-encapsulated bulk C60.
Through the observation of photopolymerization, we speculate the movement of C60s
inside the SWNT, which is unique to the peapod structure. The polymerization conditions
are monitored by the intensity of Ag(2) vibrational mode by Raman spectroscopy. The
photopolymerization processes is accelerated under higher laser intensity in the case of
bulk C60. On the other hand, encapsulated C60 have never been completely polymerized
even under the threshold power that causes an ablation. However the spectral shape is
broadened as the higher incident laser intensity is applied. By tracking the time
dependence intensity ratio of monomer and polymer Raman peaks, C60 molecules and its
origomers have a freedom to attach and detach with their neighbors assisted by the
interaction with the SWNT walls. Because of this freedom of C60, the fabrication of a
complete polymer chain inside SWNT is a vicious circle.
60
MELAMINE-FORMALDEHYDE MICROCAPSULES CONTAINING
EUCALIPTUS ESSENTIAL OIL FOR FOOTWEAR APPLICATIONS
65
Abstracts
M. M. Sánchez Navarro, F. Arán Aís, C. Orgilés Barceló, Footwear
Research Institute INESCOP, Pol. Ind. Campo Alto 03600 Elda Alicante
Spain, [email protected]
The situation of the industry today makes it necessary for new materials and concepts to
be found, to be used as differentiating elements against competitors and to make products
stronger in terms of quality, personal health and safety, or respect for the environment. In
this sense, microencapsulation presents a new option for the shoe industry as its
application can transform traditionally used materials or products into smart materials or
products capable of interacting with feet. They can improve quality of life by
incorporating therapeutic products for foot care such as properly dosed essential oils. The
microencapsulation of active substances to be incorporated in different footwear
components in order to obtain an "active shoe" presents an opening up of a new way of
innovation. The eucalyptus essential oil is obtained from the leaves and the branches of
the eucalyptus tree, 'Eucalyptus globulus'. The main active ingredient in eucalyptus oil is
"eucalyptol" which has strong germicidal and disinfectant properties. Eucalyptus oil has
an analgesic effect and is often used in preparations designed to relieve muscle, nerve and
joint pains. Commonly, a mixture of the eucalyptus oil with almond oil is used in order to
reduce the chance of irritation that the use of eucalytus oil alone could cause. Almond oil
is a natural moisturizing agent very often used in the cosmetic industry due to its high
essential oil content such as oleic and linoleic oils. Because it is not greasy, it is absorbed
quickly. The polymerization in situ allows the formation of microcapsules containing
water-immiscible dispersed phase, with improved mechanical properties and thermal
stability. The properties of the membrane depend not only on its chemical structure but
also on all the synthesis conditions. The polycondensation of the amino resin occurs in
the continuous phase, and the phase separation is linked to the pH and the
formaldehyde/melamine molar ratio. In this study a series of melamine-formaldehyde
(MF) microcapsules containing a mixture of eucalyptus essential oil and almond oil was
prepared by an in-situ polymerization (O/W) method to be applied to footwear materials
(lining, insoles, etc…). The O/W emulsions were prepared by means of a Branson
sonifier in order to obtain smaller sized droplets and therefore smaller MF microcapsules,
near 1µm. In this study, the effect of the MF resin/ oil ratio and the influence on its
structural and thermal properties of the resultant microcapsules were studied. The surface
morphology and chemical structure of the microcapsules were investigated using an
optical and scanning electron microscope (SEM), and Fourier-transform infrared analysis
(FT-IR), respectively. The thermal properties of the samples were investigated by
differential scanning calorimetry (DSC). The microcapsules size was measured using a
Coulter size analyser.
SLOW RELEASE OF BIOCIDE FROM SILICA MICROPARTICLES IN
WOOD PAINT
Gitte Sørensen1, Søren Poulsen2, Holger Nissen3, Anne Louise Nielsen1 and
Sune D. Nygaard1; 1Danish Technological Institute, Aarhus, 8000, Denmark;
2
Dyrup A/S – R&D Wood Care, Søborg, 2860, Denmark; 3Velux A/S WResearch & Development – Materials, Østbirk, 8752, Denmark.
[email protected]
61
66
Abstracts
During the last decades more and more attention has been paid to the environmental effects
of biocides which has resulted in more and stricter legislation on the use of biocides. To
follow this movement the industry has to develop new and environmentally friendly ways to
protect their products against microbial spoilage and the coatings industry is a part of this
movement along with other industries. An important aspect of using biocides in coatings is
the undesired high release of biocide to the environment. By changing the traditional way of
adding biocide to wood paint this high biocide release can be minimized. Nowadays,
biocide is dissolved in a small amount of organic solvent which is mixed into the wood
paint. After application to wood this often leads to a burst release of biocide from the paint
resulting in i) environmental contamination, and ii) disappearance of the biocidal effect
sooner than desired. Furthermore, more biocide than needed is added to the wood paint. In
order to avoid these problems microparticles of silica containing the biocide 3-iodoprop-2ynyl N-butylcarbamate (IPBC) have been synthesized. By encapsulating IPBC the initial
release of IPBC is slowed down, thereby minimizing release of biocide to the environment.
Intelligent synthesis of the microparticles containing IPBC enables a controlled release
profile for the biocide. The microparticles consist of a porous silica shell having a
hydrophilic exterior which makes the particles readily dispersible in waterborne wood
paints using no organic solvents. The hydrophobic core makes the particles able to
encapsulate hydrophobic biocides such as IPBC. Microparticles containing IPBC are
synthesized using sol-gel technology and are characterized using Focused-Ion-Beam
Scanning Electron Microscopy (FIB-SEM) and other techniques. These investigations
reveal that the particles are mainly found as spheres with diameters of 1-2 µm. Rudimentary
release profile measurements of the particles were performed in test setups by suspending
the particles in water and measuring the release of IPBC as a function of time using liquid
chromatography-mass spectrometry (LC-MS). The results show how a proportion of 50 %
of the IPBC is released to the water-phase within 24 hours whereas the rest remains
encapsulated in the particles. To evaluate the effect of the microparticles in wood paints,
several evaluation accelerated techniques are more appropriate to use, including QUV and
inhibition zone assays. For this reason accelerated weathering tests have been performed in
collaboration with the project partners, Velux A/S and Dyrup A/S. The effect of the biocide
is evaluated by inhibition zone assays and the results are compared to those obtained using
traditional wood paints containing non-encapsulated IPBC. These tests have shown positive
effect of encapsulated IPBC after UV exposure. All in all it has been demonstrated that it is
possible to encapsulate the important biocide IPBC in silica microparticles of roughly 1-2
µm in diameter. The microparticles containing IPBC have been shown to demonstrate
controlled release of IPBC in model systems and a prolonged UV resistance of the biocide
in subsequent accelerated weathering tests.
SILICA NANOPARTICLE AT AIR-WATER INTERFACES
Stocco Antonio, Zang DY, Binks BP* and Langevin D, LPS, University
Paris-Sud, 91405 Orsay, France; *Department of Chemistry, University of
Hull, UK; [email protected]
62
Fumed Silica nanoparticles (Wacker Chemie, Germany) are extensively used in many
industrial applications such as food and cosmetics. By changing the SiOH content, it is
67
Abstracts
possible to tailor the surface activity of these particles. Emulsions and foams stabilized by
these particles show extraordinary properties when compared to those stabilised by
standard surfactants. Here, we present some results regarding the air-water interfacial
properties and stabilization mechanisms in aqueous foams. At the water surface, we
propose an ellipsometric model to evaluate the contact angle and the surface coverage of
nanoparticles with different hydrophobic character. Moreover, surface tension
measurements and Brewster angle microscopy were carried out in order to elucidate the
absorption kinetics and the interfacial structure respectively. Foam dynamics was
followed by a multiple light scattering technique. Detailed information on the bubble and
particle arrengements were obtained by x-ray tomography. We can correlate the
interfacial properties with foam aging showing that the underlying principle for foam
stability depends on the surface tension γ and surface elasticity E through the Gibbs
stability criterion E > γ/2 (for stable foam).
63
IN VITRO CELLULAR PHOTOTOXICITY OF NANOCAPSULES
CONTAINING A METALLOPHTHALOCYANINE ON B16-F10
MELANOMA CELLS
Marigilson P. Siqueira-Moura1, Ana Paula F. Peti2, and Antonio C.
Tedesco2*. 1Prog. P.G. em Ciências Farmacêuticas, Faculdade de Ciências
Farmacêuticas-RP, Universidade de São Paulo, Ribeirão Preto-SP, Brasil;
2
Depto. Química, Faculdade de Filosofia, Ciências e Letras-RP, Laboratório
de Fotobiologia e Fotomedicina, Universidade de São Paulo, Ribeirão PretoSP, Brasil*; [email protected]
The purpose of this work was to assess the photocytotoxic effect of Chloroaluminum
Phthalocyanine (ClAlPc) encapsulated into nanocapsules (NC), and in its free form on
mouse melanoma cells (B16-F10). NC were prepared according to interfacial polymer
deposition after solvent displacement method. The phototoxicity assay was carried
following 3 h cell incubation with free, and ClAlPc-NC at 0.50 µmol.l-1. In the
phototoxicity studies cells were irradiated by a laser (wavelength 675 nm, output power
100 mW, fluence rate 14 mW.cm-2) at light doses of 20,100, and 500 mJ.cm-2. After 24 h,
the cell viability was verified by standard MTT assay. For the evaluation of the chemical
toxicity on B16-F10 cells in darkness conditions, were treated with ClAlPc (free and NC)
at a concentrations of 0.50, 1.00, and 5.00 µmol.l-1. The concentrations of 0.50 and 1.00
µmol.l-1 did not show dark toxicity for both free ClAlPc and NC while at the highest
concentration used it was observed a significant toxicity (p < 0.001). The lower
concentration was chosen to be used throughout light toxicity assay. The phototoxic
effect of free and encapsulated ClAlPc showed to be light dose dependent. The
photodynamic damage was higher for irradiated cells with ClAlPc-NC than free drug (p <
0.05). Cellular viability decreases with the increase of light dose ranging from 84.3%
(±8.64) to 21.6% (±1.30) for free ClAlPc, and from 62.0% (±5.69) to 8.4% (±0.82) for
NC both at 20 and 500 mJ.cm-2, respectively. The treated cells with ClAlPc-NC at the
highest light dose presented a cell survival fraction about 3-fold lower than that observed
for free ClAlPc. This result could be explained by the better interaction between cells and
nanocarrier leading to a higher accumulation of NC into target cells, as well as greater
68
Abstracts
photocytotoxic effect due to reactive oxygen species generated. In summary, these
findings indicate that ClAlPc-NC present an excellent phototoxicity on B16-F10
melanoma cells confirming potential of NC as drug delivery system applied to therapy
against this kind of skin cancer, until now not treated by Photodynamic Therapy.
Financial support: Grants from FAPESP 07/55319-0, 08/53719-4, 07/58809-9
(M.P.S.M.), and CNPq 101703/2008-2 (A.P.F.P.).
LAYERED DOUBLE HYDROXIDE NANOCRYSTALS LOADED WITH
EXCHANGEABLE ANIONS FOR CONTROLLED CORROSION
PROTECTION
João Tedim1, Mikhail Zheludkevich1, Alena Kusnetzova1, Andrei Salak1 and
Mário Ferreira1,2; 1University of Aveiro, CICECO, Dep. Ceramics and Glass
Eng., 3810-193, Aveiro, Portugal; 2Technical University of Lisbon, IST,
ICEMS, Av. Rovisco Pais 1049-001 Lisbon, Portugal; [email protected]
64
The quest for inert nanomaterials (nanoparticles, nanowires, nanosheets) able to provide
controlled release of species is nowadays a hot-topic in pharmaceutical areas, with the socalled drug-delivery systems. Nevertheless, this concept is transversal to a large number
of fields, including corrosion science. Following the banishment of carcinogenic
chromium (VI) species, demands for “greener” technological solutions with the same (or
superior) level of metal protection soon appeared. Different scientific and industrial
groups are currently focused on the development of nanostructured systems capable to
efficiently protect metals against corrosion by controlling the local release of inhibiting
species where corrosion has started or is about to start. Here we report the synthesis and
characterization of Layered Double Hydroxides (LDHs) with general formula [M2+13+
nxM x(OH)2]A x/n.mH2O. These systems are also called anionic clays and consist of
stacks of positively charged, mixed metal hydroxides separated by galleries where
anionic species and solvent molecules can be intercalated. The goal is to load these
inorganic host structures with inorganic and/or organic corrosion inhibitors, so the LDHs
will act as nanocontainers with two main roles: (i) release of corrosion inhibitor upon
triggering conditions in the surroundings (e.g. pH changes, presence of aggressive
species) and (ii) entrapment of detrimental anions to the metal substrates such as Cl- and
SO42-. LDHs are prepared by anion-exchange and the resulting particles are analysed by
X-ray diffraction and electron microscopies. Different parameters are investigated,
including the effect of temperature and time of hydrothermal treatment on particle size
and stability of aqueous suspensions. Subsequently, electrochemical techniques are used
to assess the anticorrosion capabilities of these systems with respect to different metal
alloys, namely hot dipped galvanised steel and aluminium 2024. As a result, LDHs
loaded with corrosion inhibitors were found to impart corrosion protection upon metallic
substrates in contact with NaCl aqueous solutions.
69
Abstracts
SELF-ASSEMBLY OF MULTI-STIMULI RESPONSIVE COPOLYMERS
Klaus Tauer,1 Nancy Weber,1 and John Texter, 1,2, 1Max lanck Institute for
Colloids and Interfaces, 14624 Golm (Potsdam), Germany; 2Schol f
Engineering Technology, Eastern Michigan University, Ypsilanti, MI 48197
USA; [email protected] 65
Ionic liquids (ILs; organic salts with melting points less than 100°C) and polymers of
ionic liquid monomers (PIL) are exhibiting diverse uses in various types of chemical
synthesis, electrochemical applications requiring high polarization, and alternative
solvation while exhibiting high chemical and thermal stability and virtually no vapor
pressure. The combination of such polymerized ILs with other monomers and materials
are providing diverse porous materials including polyelectrolyte membranes suitable for
fuel cells and fast ion batteries, superstable latexes for new classes of organic coatings
and composite films of nanocarbon, and diverse nanoparticle suspensions. The anion and
solvent stimuli responsiveness of such IL-based materials provide chemical and physical
switches around which new materials and processes may be designed.
Core-shell reversible particle precipitation from aqueous di-stimuli-responsive diblocks
composed of an ionic liquid (ILBr) block and an N-isopropyl acrylamide (NIPAM) block is
demonstrated, whereby heat produces ultrastable particles with a polyNIPAM core and
excess bromide produces stable particles with a polyILBr core, as is the sequential
interconversion from the first cited core-shell combination to the other.
HYBRID PLASMONIC COLLOIDAL NANOSTRUCTURES
Benjamin Thierry, Ian Wark Research Institute, University of South
Australia, Mawson Lakes, Australia, SA 5095;
[email protected]
66
Plasmonic nanoparticles and nanorods, made of noble metals such as gold and silver, are
arguably among the most promising nanomaterials due to their surface plasmon
resonance (SPR) enhanced light scattering and adsorption. Gold nanorods are of
particular interest as their plasmonic resonance can be easily tuned from the visible to the
near-infrared (NIR) by changing their aspect ratio. The intrinsic optical properties of gold
nanorods have been exploited to design various novel in vitro and in vivo diagnostic and
therapeutic strategies based on light scattering, two-photon fluorescence, photoaccoustic
70
Abstracts
effect, optical coherence tomography, and photothermal effect. A critical requirement
towards their successful integration into functional nanodevices is the need for optimal
surface functionalization procedures.
Towards the design of a robust and universal gold nanorods functionalization procedure,
we report here the use of an intermediate polymeric layer that acts as a steric stabilization
agent during ligand exchange procedures. To demonstrate the versatility of this novel
approach, gold nanorods have been functionalized with various ω-substituted alkanethiols
such as 11-mercaptoundecaonic acid (MUA), 3-amino-5-mercapto-1,2,4-triazole,
dodecanethiol and 3-mercaptopropyl-trimethoxysilane (MPTS). Partial functionalization
at the gold nanorods ends with alkanethiol molecules such as MUA is usually observed
due to preferential binding of thiols to the Au{111} surface due to the lower coverage of
hexadecyltrimethylammonium bromide (CTAB). Taking advantage of the steric
protection provided by a polyethyleneglycol layer, complete removal of the CTAB
bilayer could be obtained in this work without impacting on the colloidal stability of the
gold nanorods as shown by X-ray photoelectron spectroscopy, transmission electron
microscopy and UV-vis measurements.
The creation of well-defined functionalized interfaces enabled the manipulation, selfassembly and integration of the gold nanorods into complex multifunctional
nanostructures. MPTS functionalization afforded vitreophilic nanorods that could be
easily encapsulated within a silica shell and further loaded with fluorescent and Raman
dyes. Hydrophobized nanorods displayed typical self-assembly features and have been
integrated into hybrid plasmonic-micellar nanostructures that could be further loaded
with chemotherapeutics such as paclitaxel and diagnostic agents such as indocyanine. In
summary, the integration of gold nanorods into hybrid colloidal nanostructures is
described towards the design of novel plasmonic diagnostic and therapeutic strategies.
MECHANICAL PROPERTIES OF SINGLE HOLLOW SILICA
PARTICLES
Doris Vollmer1, Lijuan Zhang1, Maria D’Acunzi1, Michael Kappl1, Günter
K. Auernhammer1, Carlos van Kats2, Alfons van Blaaderen2; 1 Max Planck
Institute for Polymer Research, Mainz, Germany; 2 Soft Condensed Matter,
Debye Institute for Nanomaterials Science, Utrecht University, Utrecht, The
Netherlands; [email protected]
67
Hollow particles of micron and sub-micron dimensions are abundant in nature in the form
of bacterial or viral capsids. The shells’ mechanical properties determine their stability
and flow behavior. We investigated the mechanical properties of single silica shells by
force-distance spectroscopy. The spherical capsules of different diameters (800 nm and
1.9 µm) and shell thickness (15 nm thickness 70nm) were immobilized on a silicon
substrate. Shells thinner than 15 nm could not be analyzed because they can be
irreversibly deformed by capillary forces during drying. We probed the elastic response
of the hollow particles by applying a point load, successively increasing the load until the
shell broke. In agreement with the predictions of shell theory the deformation increases
linearly with applied force for small deformations. For thicknesses larger than 20 nm the
71
Abstracts
Young modulus is independent of shell thickness. However, it depends on the thermal
history of the sample. It increases from 10 GPa for unheated shells to close to that of
fused silica (80 GPa) after heating the hollow particles to 1100 °C. Heating transforms
the large number of silanol groups into Si-Si bonds. This transformation leads to a
compaction of the shells, which is reflected in a reduction of the diameter of the hollow
particle as well as its shell thickness. Amazingly, tempering at 1100 °C induces
smoothing of shells although the particles still remain spherical as shown by atomicforce-microscopy and scanning-electron-microscopy.
ENCAPSULATION AS A BUSINESS
Dennis M. Vriezema, Lee Ayres, Dennis Lensen, Joost A. Opsteen, Tian Pu;
Encapson BV, Toernooiveld 1, 6525 ED Nijmegen, the Netherland;
[email protected]
68
The range of applications for the use of encapsulation is numerous. Much like the
function of the cell membrane one can use encapsulation for protection, delivery,
controlled release, compartmentalization, etc. At Encapson we focus on research and
development of capsules for encapsulation in a broad range of applications. Besides
encapsulation and capsule formation we also prepare the polymers that are used for
encapsulation in-house. In this way we are able to tailor the properties of the resulting
capsules exactly to the needs of the customer and application. We can tune for instance
the (bio)degradation, release time, compatibility and permeability by varying the polymer
type, molecular weight, ratio between blocks, building in of functional groups, etc. We
are not limited to the use of only one method of encapsulation. We make use of internal
phase separation, in-situ polymerization, layer-by-layer deposition and self assembly for
e.g. the encapsulation of biomaterials, gases, catalysts and drugs, either hydrophobic or
hydrophilic. When a client is thinking of applying encapsulation in their process or when
they are interested in the benefits of encapsulation for new applications we can design
and prepare capsules filled with the desired compound for testing.
72
Abstracts
69
DEVELOPMENT OF ACTIVATED SPHERICAL PARTICLES AS A
SCAFFOLD FOR TISSUE REGENERATION
Yanhong Wen, Lene Jørgensen, Eva Horn Møller and Hanne Mørck Nielsen,
Dept. of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical
Science, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen,
Denmark; [email protected]
Scaffolds are used in tissue engineering as a structural cell support and for the delivery of
active substances for stimulation of cell growth. Natural as well as synthesized materials
have been utilized to fabricate different types of scaffolds for these purposes. The aim of
the present project is to develop optimized microspherical particles containing
therapeutically active substances for combination with autologous stem cells intended for
tissue regeneration. Variants of the polymer methoxy poly(ethylene glycol)-poly(lactide)
copolymer) (MPEG-PLGA) has been chosen as the scaffold material for the preparation
of microspheres. PLGA, which is approved by FDA as scaffold material due to its
biocompatibility and biodegradability, is modified by MPEG to obtain a more
hydrophilic and flexible surface. MPEG-PLGA microspheres were fabricated by the
emulsion-solvent evaporation method using polyvinyl alcohol (PVA) as the surfactant.
The microspheres were characterized with respect to external and internal morphology,
porosity, particle size, degradation etc. The microspheres were prepared in varying sizes
and porosities in order to optimize cell adhesion and loading/release properties. The
residual water and surfactant polyvinyl alcohol (PVA) content were controllable by using
freeze-drying. The active microspheres will be studies with cell systems of interest, in
order to optimise the microparticle characteristics to achieve the desired cellular
behaviour.
DEVELOPMENT OF AMORPHOUS DRUG NANOPARTICLES BY
NovaSperse℠ TECHNOLOGY
Deepak Thassu, PharmaNova Inc, Victor, NY, USA; Ren Xu, Beckman
Coulter Inc., Miami, FL, USA; [email protected]
70
NovaSperse℠ is a proprietary platform technology developed by PharmaNova, Inc., to
create amorphous nanoparticles of pharmaceuticals that are typically poorly watersoluble. NovaSperse℠ creates spherical nanoparticles of pure drug substances offering
enhanced solubility and numerous advantages over nano-crystals and other type of
nanoparticles.
NovaSperse℠ technology is based on solvent displacement principles with precise
control on formation of nuclei and molecular aggregates leading to desired particle sizes
with a narrow particle size distribution that is characterized by photon correlation
spectroscopy. The technology allows us to modify the nanoparticles surface properties
which facilitates stabilization of nanoparticles and helps in developing smart
nanoparticles for targeting purposes.
73
SD
Abstracts
The combined features of the NovaSperse℠ process and choices of stabilizers
characterized by the surface zeta potential of nanoparticles result in stable suspensions of
amorphous nanoparticles with good stability with small change in particle size during
storage in various conditions.
SYNHTESIS AND CONTROLLED RELEASE FROM POLYMER
MICROSPONGES,
Aleš Zadražil and František Štěpánek, Department of Chemical Engineering,
Institute of Chemical Technology Prague, Technická 5, 166 28 Prague, Czech
Republic; [email protected]
71
The aim of this work is to fabricate miniature sponge-like porous structures, which will
be able to change their local properties (porosity, pore diameter) as a result of an external
stimulus (pH, temperature, chemical composition of a solution). Thermo-responsive
hydrogels based on a poly(N-isopropylacrylamide) are used for fabrication of micro-size
spheres (in the size range of 10-100 µm). We use both liquid (acetone, ethanol) and solid
(calcium carbonate) porogens for increasing, at various length-scales, the internal
porosity of hydrogels during polymerization. The usage of porogens will lead to the
creation of conducting channels and dead-end reservoirs, which may contain bulk liquid
other than that contained in the expanded gel network. The expansion/contraction of the
porous network will, consequently, cause reversible ejection/suction of the liquid from/to
the reservoirs. In order to effectuate “remote control” of the polymer volume change,
composite structures containing Fe2O3 nanoparticles are used. Upon the application of an
external electromagnetic field, the particles can locally increase temperature and induce a
transition from the expanded to the collapsed state of the polymer. The dynamics and
extent of the polymer volume change as function of temperature was investigated by
means of digital image analysis, and the microstructure of the porous network was
visualized by SEM and x-ray microtomography. The kinetics of controlled release of
model active substances from the micro-sponges has been investigated by time-dependent
UV/VIS spectrophotometry. Applications of these active micro-sponges include targeted
delivery or absorption of active ingredient in various complex environments of both
biological and inorganic origin.
72
FACILE AND CONVERGENT SYNTHESIS OF POLYMER-COATED
GOLD NANOPARTICLE LIBRARIES
Matthew I. Gibson and Harm-Anton Klok*, Laboratoire des Polymères,
Institut des Matériaux, Ecole Polytechnique Federale de Lausanne (EPFL),
Station 12, Lausanne, CH-1015, Switzerland. [email protected]
In recent times the application of nanomaterials in biology and medicine has increased
greatly. However, there is still a need for methods to synthesise well-defined
nanoparticles of predictable size and surface functionality, in a readily accesible manner.
74
Abstracts
In this presentation, we present a new, two step strategy for the convergent synthesis of
polymer-coated nanoparticle libraries, with precise control over the size and surface
functionality of the particles. The first step involves the post-polymerization modification
of a reactive polymer precursor to give a diverse polymer library from a small number of
“master” templates. The polymers are synthesized in such a manner as to incorporate an
orthogonal handle at one chain end, which can be used to, in a second step, tether the
polymers onto preformed inorganic cores to give a brush-like surface coating. Starting
from just 3 precursor polymers and 3 different sized particle cores, we synthesized a
large, 75 member nanoparticle library, where the particle size is controlled by the
inorganic core and the molecular weight of the polymer precursor and the functionality
by the polymer coating. The library has also been used to evaluate the influence of
particle structure on aggregation in various biologically relevant media. This facile
method for nanoparticle synthesis will be useful to rapidly access model nanoparticles for
structure-property relationships.
Scheme 1. Covergent synthesis of nanoparticle libraries via post-modification reactions.
73
ASSEMBLY OF BIOINSPIRED, NANOENGINEERED MATERIALS FOR
TARGETED DRUG DELIVERY
Angus P. R. Johnston, Lillian Lee, Christina Cortez and Frank Caruso,
Department of Chemical and Biomolecular Engineering, The University of
Melbourne, Parkville, Melbourne, Australia 3010; [email protected]
Targeted delivery of drugs to specific cells in the body has the potential to improve the
treatment of many illnesses, including cancer and HIV. An emerging technique to deliver
drugs is by immobilising the drug inside a nanocapsule, whereby the body is protected
from potentially harmful side effects of the drug, while also preventing the drug from
being degraded by the body. One way to prepare these capsules is by the layer-by-layer
deposition of interacting polymers onto a sacrificial template particle. This technique
allows for fine control over the properties of the capsule by altering the number of layers
deposited, the material deposited at each layer, and also by controlling the assembly
conditions. However, assembly of structures on the nanoscale requires fine control of the
75
Abstracts
assembly process. DNA provides an ideal building block for such films, as it is
biocompatible and the complementary base paring can be used to facilitate assembly of
the film as well as induce structures into the film on a nanoscale. We show that stable,
responsive DNA capsules can be synthesised and the properties of the film can be
controlled using different DNA sequences. We also show that nanocapsules can be
targeted specifically to colorectal cancer cells by modifying the surface of the capsule
with an antibody.
74
FORMATION OF SMART NANOCAPSULES FOR DEFINED SLOW OR
SUDDEN RELEASE
Anna Musyanovych and Katharina Landfester; Max Planck Institute for
Polymer Research, 55128 Mainz, Germany;
[email protected]
A growing interest in the engineering of polymeric nanoparticles as specific carriers for
drugs and imaging agents is generally focused on their tissue permeability. Especially an
increased attention has gained to core-shell particles consisting of a liquid core owing to
their utilization as sub-micrometer containers for the encapsulation of biologically active
substances. The ideal nanocarrier will be one that is size and morphology specific, has the
ability to encapsulate variety of compounds, could be functionalized with certain surface
targeting ligands, and has the possibility to be delivered and to release the encapsulated
material in a controlled way. Significant benefits of the miniemulsion technique offer
formation of polymeric biocompatible/biodegradable capsules in the sub-micron size
range with oil or aqueous core and different wall thickness. The main principle based on
the formation of stable liquid-in-liquid immiscible miniemulsion droplets. The high
stability of the droplets gives an opportunity to perform the reactions within the droplets
or at their interface. Due to the lack of monomer diffusion processes throughout the
polymerization, an efficient encapsulation can be obtained by phase separation inside the
nanodroplets throughout the polymerization process, by nanoprecipitation of the polymer
onto nanodroplets, or by an interfacial reaction at the nanodroplet’s interphase. As an
example, biodegradable nanocapsules (size range 250 – 600 nm) with encapsulated
dsDNA (790 base pairs) were produced via anionic polymerization of nbutylcyanoacrylate (BCA) carried out at the interface of homogeneously distributed
aqueous droplets in the inverse miniemulsion. Fluorescent polyurea and crosslinked
starch nanocapsules were synthesized by polyaddition reaction between the water-soluble
diamine (or starch) and oil-soluble diisocyanate at the water-oil interface. Biodegradable
poly(L-lactide), poly(ε-caprolactone), and poly(lactide-co-glycolide) particles have been
obtained from the preformed polymer by combination of miniemulsion and solvent
evaporation techniques, based on the precipitation of the polymer within the
miniemulsion droplets and subsequent encapsulation of the hydrophobic material.
Different triggers can be used for a slow or fast release of materials out of the
nanocapsules.
76
Abstracts
FORMATION OF SMART NANOCAPSULES FOR DEFINED SLOW OR
SUDDEN RELEASE
Anna Musyanovych and Katharina Landfester; Max Planck Institute for
Polymer Research, 55128 Mainz, Germany;
[email protected]
74
A growing interest in the engineering of polymeric nanoparticles as specific carriers for
drugs and imaging agents is generally focused on their tissue permeability. Especially an
increased attention has gained to core-shell particles consisting of a liquid core owing to
their utilization as sub-micrometer containers for the encapsulation of biologically active
substances. The ideal nanocarrier will be one that is size and morphology specific, has the
ability to encapsulate variety of compounds, could be functionalized with certain surface
targeting ligands, and has the possibility to be delivered and to release the encapsulated
material in a controlled way. Significant benefits of the miniemulsion technique offer
formation of polymeric biocompatible/biodegradable capsules in the sub-micron size
range with oil or aqueous core and different wall thickness. The main principle based on
the formation of stable liquid-in-liquid immiscible miniemulsion droplets. The high
stability of the droplets gives an opportunity to perform the reactions within the droplets
or at their interface. Due to the lack of monomer diffusion processes throughout the
polymerization, an efficient encapsulation can be obtained by phase separation inside the
nanodroplets throughout the polymerization process, by nanoprecipitation of the polymer
onto nanodroplets, or by an interfacial reaction at the nanodroplet’s interphase. As an
example, biodegradable nanocapsules (size range 250 – 600 nm) with encapsulated
dsDNA (790 base pairs) were produced via anionic polymerization of nbutylcyanoacrylate (BCA) carried out at the interface of homogeneously distributed
aqueous droplets in the inverse miniemulsion. Fluorescent polyurea and crosslinked
starch nanocapsules were synthesized by polyaddition reaction between the water-soluble
diamine (or starch) and oil-soluble diisocyanate at the water-oil interface. Biodegradable
poly(L-lactide), poly(ε-caprolactone), and poly(lactide-co-glycolide) particles have been
obtained from the preformed polymer by combination of miniemulsion and solvent
evaporation techniques, based on the precipitation of the polymer within the
miniemulsion droplets and subsequent encapsulation of the hydrophobic material.
Different triggers can be used for a slow or fast release of materials out of the
nanocapsules.
75
ENGINEERING PARTICLES WITH BIOINTERFACES
EMPLOYING VIRAL ARCHITECTURES
Edwin Donath, Institute of Medical Physics & Biophysics, Leipzig
University, Härtelstrasse 16/18, D-04107 Leipzig, Germany;
[email protected]
Bringing together viruses and particles, is this just a curious idea, or is there more behind
combining the properties of viral architectures with the benefits of artificial particles?
77
Abstracts
The lecture will try to give an answer to this question, discusses the ways of how to
couple viruses with particles, and outline the perspectives and areas of application. For
many, viruses have a reputation of carrying and spreading infectious and dangerous
agents. They consist of a protein coat that houses the genetic instructions for infecting
and replicating itself in living cells. For the chemist or physicist however, viruses
represent organic nanoparticles with interesting properties and functions. Viruses, which
are assembled from proteins and nucleic acids into precise structures and topologies, can
be engineered into attractive building blocks for various applications in novel
nanocomposite materials. Their area of application ranges from technical devices to
particle-based diagnostic assays and drug delivery. The co-localization of the viral
genome representing the construction plan within the self-assembled viral particle offers
enormous possibilities for molecular-biology-based engineering. If the genetic sequences
encoding for the structural components of viruses are inserted into plasmids and
expressed in cells it is possible to obtain virus-like particles that do not carry genetic
material, and, thus, can be safely applied in materials and particle technologies. They can
be produced employing culture cells as factories for mass-production. Attaching viruses
onto particle surfaces requires proper techniques. Many viruses additionally carry a lipid
envelope with proteins responsible for the entry of viruses into cells employing
membrane fusion triggered by pH changes. Mimicking this natural infection pathway is
one way of integrating viruses into the surface of lipid coated particles. The lipid layer
has a dual function i) serving as the support for the viral elements, and ii) providing the
particle surface with biocompatible properties. Engineering the capsid proteins of viruses
with tags with a specific affinity for selected materials is another way of fabricating
hybrid structures. In the lecture both ways will be illustrated with recent results from the
work of author`s and from other groups. The outstanding performance of these structures
will be demonstrated with recent examples, where virus-engineered particles and surfaces
have been used in diagnostic assays.
NANOCONTAINERS WITH CONTROLLED PERMEABILITY FOR
FEEDBACK ACTIVE COATINGS
Dmitry G. Shchukin, Department of Interfaces, Max-Planck Institute of
Colloids and Interfaces, Am Mühlenberg 1, D14476 Golm, Germany;
[email protected]
76
The new multifunctional coatings should combine passive components inherited from
"classical" coatings and active components, which provide fast response of the coating
properties to changes occurring either in the matrix of multifunctional coatings (e.g.,
cracks, local pH change) or in the local environment (temperature, humidity). Recent
level of the surface science shows new opportunities for fabrication of active feedback
coatings through the integration of nanoscale containers or continuous networks loaded
with the inhibitor into coating matrix thus designing completely new coating of the
"passive" host - "active" guest structure. The main idea here is to use nanocontainers with
a shell possessing controlled permeability properties. As a result, nanocontainers are
uniformly distributed in the passive matrix keeping active material in "trapped" state thus
avoiding the undesirable interaction between active component and passive matrix and
spontaneous leakage. When the local environment undergoes changes or if the active
78
Abstracts
surface is affected by the outer impact, the nanocontainers respond to this signal and
release encapsulated active material.The most important task is to develop
nanocontainers with good compatibility with the matrix components, the possibility to
encapsulate and upkeep active material and permeability properties of the shell controlled
by external stimuli. The nanocontainers should also be of a size less than 300-400 nm; the
nanocontainers of larger size can damage the integrity of the coating matrix forming large
hollow cavities, which reduce the passive protective properties of the coating. Depending
on the nature of the sensitive components (e.g., weak polyelectrolytes, metal
nanoparticles) introduced into the container shell, reversible and irreversible changes of
the shell permeability can be induced by various stimuli: changes of pH, ionic strength,
temperature, ultrasonic treatment, alternating magnetic field, electromagnetic irradiation.
Different responses can be then observed varying from fine effects like tunable
permeability to more drastic ones like total rupture of the container shell. There are two
mostly versatile approaches for preparation of the “intelligent” nanocontainers for
feedback active coatings. A first one comprises layer-by-layer assembly of oppositely
charged species on the outermost surface of the porous particles and nanotubes using
polyelectrolytes, conductive polymers, biopolymers, and nanoparticles as constituents of
the nanocontainer shell. Second approach involves the use of ultrasonic waves to
fabricate inorganic and composite hollow nanospheres. In this case, a cavitation interface
is employed as a reaction zone where a sensitive shell is formed from organic precursors
or pre-formed nanoparticles adsorbed at the gas/liquid interface via polycondensation,
polymerization, and particle melting (or sonoinduced welding). Ultrasonic synthesis can
result in hollow spheres containing either water-immiscible or water-miscible liquid in
their inner cavity.
EMULSION BASED ENCAPSULATION
Heidi Johnsen, Stephan Kubowicz, Per Stenstad, Lars Kilaas and Ruth
Schmid. SINTEF Materials and Chemistry, NO-7465 Trondheim, Norway;
[email protected]
77
Encapsulation in micro- and nanoparticles is an effective method for protection and
controlled release of liquid and solid substances. There are numerous preparation
methods available for producing particles and capsules. An important issue is the reliable
and reproducible preparation by industrially scalable methods. The products and the
processes must be technically feasible and affordable. The emulsion based method called
“miniemulsion polymerisation” is an inexpensive process which is suitable for up-scaling
to industrial production. Both liquids and solids can be encapsulated by miniemulsion
polymerisation, provided that they do not interfere with the polymerisation process. The
key feature of the miniemulsion process is the co-stabilizer added to the droplet phase
before emulsification, as it stabilizes the system against Ostwald ripening. Miniemulsion
polymerisation has been applied successfully for encapsulation of active compounds for
agricultural products, cosmetics, personal care and household products, as well as in
biomedical applications. Examples of encapsulated substances are liquid crystals,
magnetic iron oxides, insect repellents and fragrances. Our current aim is to adapt the
method for encapsulation of drugs and diagnostic markers in biocompatible and
biodegradable polymers. The miniemulsion polymerisation technique has been applied to
79
Abstracts
prepare nanoparticles of the biodegradable polymer poly(butyl-2-cyanoacrylate) (PBCA).
For medical application as drug delivery system, characteristics of the nanoparticles
surface are crucial to avoid clearance by the reticuloendothelial system. Therefore, to
inhibit unspecific binding to cells in general, and to prevent an uptake by monocytes,
nanoparticles having poly(ethylene glycol) chains at the surface have been synthesized.
General Session 6
AMPHIPHILIC CORE-SHELL PARTICLES IN ADVANCED
WASTEWATER TREATMENT TECHNOLOGY
Pei Li,1 Chi Ho Fan,1,2 Jasper Choy,2 Ir Daniel M. Cheng2; 1 Department of
Applied Biology and Chemical Technology, The Hong Kong Polytechnic
University, Hung Hom, Kowloon, Hong Kong; 2 Dunwell Enviro-Tech
(Holdings) Ltd., 8 Wang Lee street Yuen Long Industrial Estate, Yuen Long,
New territories. Hong Kong, P. R. China; [email protected]
78
Numerous scientific forecasters have predicted that shortage of clean water is going to be
one of the biggest issues that humanity will have to face in the near- and medium-term
future. China is in danger of being one of places hardest hit by problems that will
inevitably come. Thus novel processes that can clean wastewater effectively are going to
be in great demand. Through collaboration between the University and local industrial
company, we have developed a new nanotechnology-based wastewater treatment system
through combining novel amphiphilic core-shell particles and vibratory shear enhanced
process (VSEP). The new polymer particles have functional hydrophilic shells and welldefined hydrophobic cores with particle sizes in nano- to submicro-scales. The unique
core-shell design of the particles enables the shell to adsorb most of the organic and
inorganic contaminants found in industrial wastewater and materials leached from
landfills, while the core acts as a solid support for subsequent separation from the water.
The nanoparticles, once saturated by contaminants, can be separated from the liquid by
vibrating ultra-filtration systems. The recovered particles can be easily regenerated
through simply changing the solution pH. Thus the re-activated particles can be used
repeatedly without affecting their capacity to remove the targeted compounds. The
regenerability of the core-shell nanoparticles is a new breakthrough which leads to a costeffective zero discharge water treatment process. In addition, this novel wastewater
treatment technology may replace the reverse osmosis (RO) technique because it is much
simpler, more environmentally friendly process at a significantly lower operating cost.
General Session 6
ENCAPSULATION APPROACHES IN ADVANCED DISPLAY
TECHNOLOGY
Simona Margutti, Fraunhofer IAO, Nobelstr. 12, 70569 Stuttgart, Germany,
[email protected]
79
Electronic paper, also called e-paper, is a display technology designed to mimic the
appearance of ordinary ink on paper. Unlike a conventional flat panel display, which uses
a backlight to illuminate its pixels, electronic paper reflects light like ordinary paper and
80
Abstracts
is capable of holding text and images, allowing the image to be changed later.
The most representative examples of electronic paper are the technologies, introduced in
the beginning of 2000, by the corporations E-INK and Gyricon. A common point of the
developed technologies is the use of microencapsulated, electrically polarized particles.
Examples of commercial electrophoretic displays include the high-resolution active
matrix displays used in the Amazon Kindle, Sony Librie, Sony Reader, and iRex iLiad ereaders. These displays are constructed from an electrophoretic imaging film
manufactured by E Ink Corporation.
The main limitations of the E-INK and Gyricon approaches are the reduced application
fields and the bichromality which could only overcome employing color filters.
With the aim of getting over the intrinsic limitation of the today´s existing technologies,
Fraunhofer Gesellschaft researchers in collaboration with the University of California
Riverside (UCR) developed a technology based on microencapsulated colloidal photonic
crystals. Characteristics of the encapsulated system are its memory effect and the notrequired insertion in electronic circuit thus leading to broad applicability.
The E-Ink and Gyricon systems will be described together with forthcoming technologies
developed at Fraunhofer Gesellschaft and UCR.
General Session 6
OPTICALLY ADDRESSABLE POLYMERIC MICROCAPSULES
Matthieu F. Bédard§, Andre G. Skirtach# and Gleb Sukhorukov§; §SEMS
University of London, Mile End, London, UK; Interfaces, 14424-Potsdam,
Germany; [email protected]
80
The development of novel remotely addressable tools for encapsulation, storage and
delivery of various materials at the micrometer scale is a particularly challenging topic of
material science. Using microcapsules as a drug delivery agent for instance, not only
requires the microcontainers to possess the sufficient mechanical stability or to be
delivered at the correct target cells, but they should also possess an efficient remotely
addressable release mechanism. Our aim is to develop polymeric microcontainers with
highly efficient optically addressable release properties. Gold nanoparticles and
photodynamic dyes were chosen to sensitize microcapsules for their spectral properties in
the visible and near-IR as well as for their specific responses to laser irradiation.
Microcapsules are constructed by the layer-by-layer procedure and light sensitive
materials are incorporated in the capsules shell directly during the shell construction or as
complexes with polyelectrolytes. The plasmonic band of gold nanoparticles is harvested
to optically release encapsulated substances by inducing thermo-mechanical processes
within the shell. Additionally, controlling the shape and distribution of gold nanoparticles
can significantly increase the release performance of encapsulated materials by near-IR
irradiation. Photodynamic dyes are catalysts with the ability to generate reactive oxygen
species upon irradiation, offering an alternative to metal nanoparticles as an optical
remote activation trigger. The question as to which enviromental parameters affect the
ability of microcapsules to release encapsulated substances by optical means and the
significance of these parameters in in vivo studies is also addressed.
81
Abstracts
INORGANIC ENCAPSULATION OF ORGANICS FOR IMAGING AND
DELIVERY
James H. Adair, Materials Research Institute, The Pennsylvania State
University, University Park, PA 16802, USA, [email protected]
81
Calcium phosphate nanocomposite particles (CPNPs) are a broad-based nano-platform
for both bioimaging and drug delivery. CPNPs are composed of fluorescence bioimaging
molecules and/or drugs encapsulated within a calcium phosphate matrix. Typical mean
diameter based on TEM particle counting is 20nm with a distribution range from 15 to
25nm. The CPNPs have been surface functionalized with a range of the agents including
amine, citrate, polyethylene glycol (PEG), anti-CD71, holotransferrin, and penta- and
deca-gastrin. The amine, citrate and PEG surface functionalized CPNPs have been used
to deliver a variety of drugs to cancer cells in both in vitro and in vivo studies. The
amine, citrate and PEG functionalized CPNPs are colloidally stable in a variety of
physiological environments including phosphate saline buffer (PBS, 10mM phosphate
buffered to pH 7.4 with 0.14M NaCl and 0.01m KCl) and a variety of cell culture media.
We have demonstrated that the drug-laden CPNPs are capable of delivering antineoplastic drugs to various cells including human breast and melanoma cells of a highly
hydrophobic experimental drug, ceramide. We have also shown that CPNPs undergo
dissolution after endocytosis with subsequent release of the encapsulated contents into
the cytosol (Muddana et.al, Nano Letters, 2008). Thus, the drug-laden CPNPs are an
inherently stealthy strategy to deliver active agents to cells that are drug resistant as well
as drug sensitive. Early detection is a crucial element for the timely diagnosis and
successful treatment of all human cancers, but is limited by the sensitivity of current
imaging methodologies. We have synthesized and studied bioresorbable calcium
phosphate nanoparticles (CPNPs) in which molecules of the near-infrared (NIR) emitting
fluorophore, indocyanine green (ICG), are embedded. The ICG-CPNPs demonstrate
exceptional colloidal and optical characteristics. Suspensions consisting of 16 nm average
diameter particles are colloidally stable in physiological solutions (phosphate buffered
0.15 M saline (PBS), pH 7.4) with carboxylate or polyethylene glycol (PEG) surface
functionality. ICG doped CPNPs exhibit significantly greater intensity at the maximum
emission wavelength relative to the free constituent fluorophore, consistent with the
multiple molecules encapsulated per particle. The quantum efficiency per molecule of the
ICG-CPNPs is 200 percent greater at 0.049 ± 0.003 over the free fluorophore in PBS.
Photostability based on fluorescence half-life of encapsulated ICG in PBS is 500 percent
longer under typical clinical imaging conditions relative to the free dye. PEGylated ICGCPNPs accumulate in solid, 5 mm diameter xenograft breast adenocarcinoma tumors via
enhanced retention and permeability (EPR) within 24 hours after systematic tail vein
injection in a nude mouse model. See figure below. Ex situ tissue imaging further
verifies the facility of the ICG-CPNPs for deep-tissue imaging with NIR signals
detectable from depths up to 3 cm in porcine muscle tissue. Our ex vivo and in vivo
experiments verify the promise of the NIR CPNPs for diagnostic imaging in the early
detection of solid tumors. We have also shown that the PEG-ICG-CPNPs can be used to
image pancreatic cancer with orthotopic tumors (i.e., surgically implanted in the mouse
pancreas) in the nude mouse model.
82
Abstracts
NIR images of fluorescence signals in ICG-CPNP mouse model (iii) and two controls.
From Altinoglu et.al, ACS Nano, 2008.
In addition to imaging, we have discovered that the PEG-ICG-CPNPs can be used for
tumor growth arrest based on photodynamic therapy (PDT) using the ICG as the
photosynthesizer. PDT is the treatment of diseased tissue with light in combination with
an optically active compound known as a photosentisizer. Fickweiler et.al (J.
Photochem. Photobiol. B-Biol., 1997) discovered that ICG was a photosentisizer for
PDT in vitro for cancer cells However, conventional PDT with conventional
photosentisizers suffers from undesirable side effects with systemic introduction into
patients as well as lack of deep tissue penetration. Biological degradation of the free ICG
in the bloodstream severely limits PDT to more topical, local treatment of cancer.
However, Russin et.al (to be submitted) have recently shown that the PEG-ICG-CPNPs
can be seen in the near infra-red to depths of at least 8cm. Furthermore encapsulation of
the ICG in the CPNPs protects the ICG from biological degradation during in vivo
transport to the cancer cells. The testing of the dye encapsulated nanoparticles on live
mouse models was performed by a group led by pharmacologist Mark Kester at the Penn
State Hershey College of Medicine. For xenografts of breast cancer in the nude mouse
model, tumor growth is arrested by the PDT with 3 minutes of near infra-red radiation
(l=785nm) at an intensity of 50J/cm2. In contrast, radiation treatment with 0.002J/cm2
only resulted in tumor growth arrest by 50 percent relative to controls. In preliminary
data, we show similar effects with leukemia in the nude mouse model after PDT. Thus,
photodynamic therapy combined with the nano-platform represented by the calcium
phosphate nanocomposite particles has the potential to provide new and innovative
opportunities in the identification and treatment of cancer.
83
84
Speaker and Presenter Index
(Alphabetically by Name with Abstract Number)
Adair, James; 81
Advincula, Rigoberto; 2
Akartuna, Ilke; 13
Altinoglu, Erhan; 14
Antequera-Garcia, Gema; 15
Arpagaus, Cordin; 16
Azevedo, Ricardo; 17
Bédard, Matthieu; 80
Brandau, Thorsten; 43
Burgess, Diane; 8
Choi, Won Sun; 18
Christensen, Andreas Lauge; 19
Christensen, Sune M.; 20
Dähne, Lars; 6
De Cock, Liesbeth; 21
De Geest, Bruno; 41
De Smedt, Stefaan; 5
Decher, Gero; 7
del Mercato, Loretta; 22
Dohnal, Jiri; 23
Donath, Edwin; 75
Doussineau, Tristan; 24
Erni, Philipp; 25
Fery, Andreas; 9
Giannachi, Chiara; 26
Hettrich, Kay; 27
Jantarat, Chutima; 28
Johnsen, Heidi; 77
Johnston, Angus; 73
Kamegawa, Katsumi; 29
Keck, Cornelia; 45
Klok, Harm-Anton; 72
Kokol, Vanja; 30
Kovacik, Pavel; 31
Küpcü, Seta; 32
Lee, Jonghwi; 33, 34
Lensen, Dennis; 35
Li, Pei; 78
Madarieta-Pardo, Iratxe; 36
Margutti, Simone; 79
Marison, Ian; 40
Martins, Isabel; 37
Meiners, Jean-Antoine; 47
Möhwald, Helmuth; 44
Musyanovych, Anna; 74
Mykhaylyk, Olga; 38
Nielsen, Lise Junker; 49
Ono, Tsutomu; 50
Ozalp, Veli Cengiz; 51
Poncelet, Denis; 1
Pastoriza-Santos, Isabel; 52
Piñot, Rafael Lacambra; 53, 54
Prestidge, Clive; 55
Quellet, Christian; 42
Rivera Gil, Pilar; 56
Rodrigues, Sofia; 57
Saez-Martinez, Virginia; 58
Saito, Yuika; 59
Sánchez Navarro, Magdalena; 60
Scheibel, Thomas; 10
Shchukin, Dmitry; 76
Sørensen, Gitte; 61
Stocco, Antonio; 62
Strand, Berit; 48
Sukhorukov, Gleb; 3
Tedesco, Antonio; 63
Tedim, João; 64
Texter, John; 65
Thierry, Benjamin; 66
van Herk, Alex; 11
Veršič, Ronald; 39
Vollmer, Doris; 67
Vriezema, Dennis; 68
Walther, Mathias; 4
Wen, Yanhong; 69
Xu, Ren; 12, 70
Yilmaz, Gulden; 46
Zadrazil, Ales; 71
85
86
Preregistered Conferees
James Adair
Penn State University
249A MRL Building
University Park, PA 16803, USA
[email protected]
Rigoberto Advincula
University of Houston
Chemistry-136 Fleming Bldg
4800 Cullen Boulevard
Houston, TX 77204, USA
[email protected]
Ilke Akartuna
ETH Zurich
Wolfgang-Pauli-Strasse 10, HCI G538
CH-8093 Zurich, Switzerland
[email protected]
Erhan Altinoglu
Penn State University
221 Materials Research Lab
[email protected]
Gema Antequera-García
Univerisdade de Vigo
Grupo de Química Coliodal-Unidad
Asociada CSIC
36310-Vigo, Spain
[email protected]
Francisca Arán Ais
INESCOP, Spanish Footwear
Research Institute
Poligono Industrial Campo Alto
Aptdo Correos 253
03600 Elda, Alicante, Spain
[email protected]
Cordin Arpagaus
BÜCHI Labortechnik AG
Meierseggstrasse 40
9230 Flawil, Switzerland
[email protected]
Ricardo Bentes de Azevedo
Universidade de Brasília
Campus Darcy Ribeiro, Asa Norte
Brasília, Distrito Federal, 70910-900,
Brasil
[email protected]
Jennifa Baier
Federal Institute for Materials
Research and Testing(BAM)
Unter den Eichen 44-46
12203, Berlin, Germany
[email protected]
Matthieu F. Bédard
University of London
Mile End Road
London, E1 4SO, United Kingdom
[email protected]
Thorsten Brandau
BRACE GmbH
Taunusring 50
63755 Alzenau, Germany
[email protected]
Diane Burgess
University of Connecticut
69 North Eagleville
Storrs, CT 06269, USA
[email protected]
Bob Carr
NanoSight Ltd
Amesbury, SP4 7RT, Wiltshire, United
Kingdom
[email protected]
Lai Mei Chan
PCTS Specialty Chemicals Pte Ltd
16 Joo Koon Crescent
629018 Singapore
[email protected]
87
Ping Kwong (Peter) Chan
Nipsea Technologies Pte Ltd
16 Joo Koon Crescent
629018 Singapore
[email protected]
Liesbeth De Cock
Ghent University
Harelbekestraat 72
B-9000 Ghent, Belgium
[email protected]
Michael Chavant
Syngenta
Breitenloh 5
4333 Münchwilen, Switzerland
[email protected]
Bruno De Geest
Ghent University
Harelbekestraat 72
[email protected]
Won San Choi
Korea Basic Science Institute (KBSI)
664-14 Dukjin dong 1-ga
Dukjin-gu, 561756, Jeonju, Republic of
Korea
[email protected]
Stefaan De Smedt
Ghent University
Harelbekestraat 72
[email protected]
Tsu-Wei Chou
University of Delaware
126 Spencer Lab
Newark, DE 19716, USA
[email protected]
Andreas Lauge Christensen
University of Copenhagen
Nano-Science Center
Universitetsparken 5
2100 Copenhagen East, Denmark
[email protected]
Sune M. Christensen
Nano-Science Center
2100 Copenhagen East, Denmark
[email protected]
Lars Dähne
Surflay Nanotec GmbH
Schwarzschildstrasse 8
12489 Berlin, Germany
[email protected]
88
Gero Decher
University of Strasbourg
CNRS Institut Charles Sadron
CNRS Campus Cronenbourg
23, rue du Loess
F-67034 Strasbourg, France
[email protected]
Loretta del Mercato
University of Marburg
Renthof 7
35037 Marburg, Germany
[email protected]
Chiara Dionigi
CNR Bologna
Institute for Nanostructured Materials
Via P.Gobetti, 101
40133 Bologna, Italy
[email protected]
Jiri Dohnal
Institute of Chemical TechnologyPrague
Technicka 5
16628 Prague, Czech Republic
[email protected]
Edwin Donath
Institute of Medical Physics &
Biophysics
Leipzig University
Härtelstrasse 16/18
D-04107 Leipzig, Germany
[email protected]
Louis Doorn
Givaudan
Huizerstraatweg 28
1411GP Naarden, The Netherlands
[email protected]
Tristan Doussineau
Institute of Physical Chemistry
Friedrich Schiller University of Jena
Lessingstrasse 10
D-07743 Jena, Thuringia,, Germany
[email protected]
Ellie Dowell
NanoSight Ltd
Kingdom
[email protected]
Adrian Downer
International Paint
Akzo Nobel
Stoneygate Lane
Felling
Gateshead, NE10 0JY, Tyne and
Wear, United Kingdom
[email protected]
Jing Dreher
BASF SE
GKP/D - J 550
67056 Ludwigshafen, Germany
[email protected]
Philipp Erni
Firmenich SA
7 Rue de la Bergère
1217 Meyrin 2, Geneva, Switzerland
[email protected]
Adolfo Fernandez-Valdes
Centro de Investigación en
Nanomateriales y Nanotecnología
Parque Tecnológico de Asturias
33428 Llanera, Asturias, Spain
[email protected]
Andreas Fery
Universität Bayreuth
Universitätsstrasse 30
95444 Bayreuth, Germany
[email protected]
Blythe Fortier-McGill
McGill University
Otto Maass Bldg, Rm 447
801 Sherbrooke Ouest
Montreal, H3A 2K6, Quebec, Canada
[email protected]
Nerea Garagorri-Gantxegi
Health Unit, INASMET-Tecnalia
Mikeletegi Paselaekua, 2
Tecnological Park
20009 San Sebastian (Guipuzcoa),
Spain
[email protected]
Albert Geiger
Roche Diagnostics GmbH
Im Nonnenwald 2 / Bldg 242
82377 Penzberg, Germany
[email protected]
Chiara Giannachi
Bracco Imaging SpA
Via Egidio Folli 50
20134 Milano, Italy
[email protected]
89
Urs Gonzenbach
ETH Zürich
HCI G531
Wolfgang-Pauli-Strasse 10
8093 Zürich, Switzerland
[email protected]
Thomas Gottschalk
BASF SE
J550 – GKP/D
Carl-Bosch-Strasse 38
67056 Ludwigshafen, Germany
[email protected]
Kay Hettrich
Fraunhofer IAP
Geiselbergstrasse 69
14476 Potsdam-Golm, Germany
[email protected]
Kiki Ikossi
Defense Threat Reduction Agency
8725 John J. Kingman Road
Fort Belvoir, VA 22060, USA
[email protected]
Chutima Jantarat
Prince of Songkla University
Pharmaceutical Chemistry
Hatyai 90112, Songkla, Thailand
[email protected]
[email protected]
Nuria Jimenez
Alcon Cusi SA
Camil Fabra, 58
08320 El Masnou, Barcelona, Spain
[email protected]
Heidi Johnsen
SINTEF Materials & Chemistry
Sem Saelands vei 2A
7465 Trondheim, Norway
[email protected]
90
Angus Johnston
The University of Melbourne
Chemical and Biomolecular
Engineering
Parkville
Melbourne, Victoria, 3010, Australia
[email protected]
Katsumi Kamegawa
National Institute of Advanced
Industrial Science & Technology
807-1 Shuku
Tosu, Saga 841-0052, Japan
[email protected]
Cornelia Keck
Free University Berlin
Kelchstrasse 31
[email protected]
Harm-Anton Klok
Ecole Polytechnique Fédérale de
Lausanne
STI-IMX-LP, MXD 112
1015 Lausanne, Switzerland
[email protected]
Dragutin Knezic
Vertex Pharmaceuticals
130 Waverly Street
Cambridge, MA 02139 ,USA
[email protected]
Tuomas Koiranen
Fermion Oy Orion Group Ltd
Koivu-Mankkaantle 6 A
FI-02101 Espoo, Finland
[email protected]
Vanja Kokol
University of Maribor
Institute of Engineering Materials &
Design
Smetanova ul. 17
SI-2000 Maribor, Slovenia
[email protected]
Pavel Kovacik
Technicka 5
[email protected]
Seta Küpcü
Universität für Bodenkultur
Center for Nanobiotechnology
Gregor Mendel Strasse 33
1180 Vienna, Austria
[email protected]
Klaus Last
Follmann & Co
Karlstrasse 59
32423 Minden, Germany
[email protected]
Jonghwi Lee
Chung-Ang University
221 HeukSeok-Dong, DongJak-gu
Seoul, 156-756, Korea
[email protected]
Dennis Lensen
Radboud University
Toernooiveld 1
6525 ED Nijmegen, The Netherlands
[email protected]
Pei Li (Pauline)
Applied Biology & Chemical
Technology
Hong Kong Polytechnic University
Hung Hom, Kowloon
Hong Kong, P. R. China
[email protected]
Iratxe Madarieta-Pardo
Tecnological Park
Spain
[email protected]
Nishil Malde
Surface Measurement Systems
5 Wharfside, Rosemont Road
London, HA0 4PE, United Kingdom
[email protected]
Andrew Malloy
NanoSight Ltd
Kingdom
[email protected]
Simona Margutti
Fraunhofer IAO
Nobelstrasse 12
D-70569 Stuttgart, Germany
[email protected]
Ian Marison
Dublin City University
Glasnevin
Dublin 9, Ireland
[email protected]
Melanie Martin
265 Clover Street
Rochester, NY 14610, USA
[email protected]
Isabel Martins
University of Porto
Rua Dr. Roberto Frias s/n
Edificio E, Piso 4, sala E413
4200-465 Porto, Portugal
[email protected]
Jean-Antoine Meiners
Micro Capsule Concepts sa (MCC)
Av de la Gare 6a
2013 Colombier, Switzerland
[email protected]
91
Helmuth Möhwald
Max-Planck-Institute for Colloids &
Interfaces
Am Mühlenberg 1
14476 Potsdam-Golm, Germany
[email protected]
Lars Folke Olsen
University of Southern Denmark
Biochemistry and Molecular Biology
Campusvej 55
5230 Odense, Denmark
[email protected]
Rainer H. Müller
Free University Berlin
Department of Pharmacy
Kelchstrasse 31
[email protected]
Tsutomu Ono
Okayama University
3-1-1 Tsushima-naka
Okayama 700-8530, Japan
[email protected]
Anna Musyanovych
Max Planck Institute for Polymer
Research
Ackermannweg 10
55128 Mainz, Germany
[email protected]
Emilio Ortiz-Alba
Centro de Investigación y Desarrollo
Tecnológico
Paseo de los tamarindos 400-B, Piso 3
Bosques de les Lomas
Mexico, Distrito Federal 05120,
Mexico
[email protected]
Olga Myhaylyk
Technische Universität München
Klinikum rechts der Isar
Institute of Experimental Oncology &
Therapy Research
Ismaninger Strasse 22
81675 Munich, Germany
[email protected]
Veli Cengiz Ozalp
Campusvej 55
[email protected]
Anne Louise Nielsen
Danish Technological Institute
Kongsvang Allé 29
8000 Aarhus, Denmark
[email protected]
Isabel Pastoriza-Santos
Departamento de Quimica Fisica,
Unidad Asociada CSIC-Universidade
de Vigo
Lagoas-Marcosende
Vigo, 36310, Spain
[email protected]
Lise Junker Nielsen
Campusvej 55
[email protected]
Christine Oliver
CSIRO-Food Science
671 Sneydes Road
Melbourne, 3030, VIC, Australia
[email protected]
92
Rafael (Lacambra) Piñol
Instituto de Ciencias de Materiales de
Aragon
Plaza de San Francisco s/n
50009 Zaragoza, Spain
[email protected]
Denis Poncelet
ENITIAA
Rue de la Géraudière, BP 82225
44322 Nantes, France
[email protected]
Clive Prestidge
Ian Wark Research Institute
University of South Australia
Mawson Lakes Boulevard
Adelaide, 5095, South Australia,
Australia
[email protected]
Christian Quellet
Givaudan Schweiz AG
Ueberlandstrasse 138
CH-8600 Dubendorf, Switzerland
[email protected]
Pilar Rivera Gil
University of Marburg
Renthof 7
35037 Marburg, Germany
[email protected]
Sofia Rodrigues
University of Porto
Rua Dr. Roberto Frias s/n
Edificio E, Piso 4, sala E413
4200-465 Porto, Portugal
[email protected]
Virginia Saez-Martinez
Tecnological Park
Spain
[email protected]
Yuika Saito
Applied Physics
Osaka University
2-1 Yamadaoka
Suita, Osaka, 565-0871, Japan
[email protected]
Magdalena Sánchez Navarro
INESCOP, Spanish Footwear
Research Institute
Poligono Industrial Campo Alto
Aptdo Correos 253
03600 Elda, Alicante, Spain
[email protected]
Thomas Scheibel
Universität Bayreuth
Universitätsstrasse 30
95440 Bayreuth, Germany
[email protected]
Dmitry Shchukin
Max Planck Institute of Colloids &
Interfaces
Am Mühlenberg 1
14476 Golm, Germany
[email protected]
Gitte Sørensen
Danish Technological Institute
Kongsvang Allé 29
8000 Aarhus, Denmark
[email protected]
Roongnapa Srichana
Prince of Songkla University
Kanjanavanich Road
Hatyai 90110, Songkla, Thailand
[email protected]
Antonio Stocco
Universite Paris-Sud
Laboratoire de Physique des Solides
91405 Orsay cedex, France
[email protected]
Berit Strand
Norwegian University of Science &
Technology
Sem Saelandsvei 6/8
N-7491 Trondheim, Norway
[email protected]
93
Philip Sturzenegger
ETH Zürich
HCI G531
Wolfgang-Pauli-Strasse 10
8093 Zürich, Switzerland
[email protected]
Gleb Sukhorukov
Queen Mary College
University of London
Mile End Road
London, E1 4NS, United Kingdom
[email protected]
Honghao Sun
Risø, Technical University of Denmark
Micro & Nanotechnology
4000 Roskilde, Denmark
[email protected]
Antonio Tedesco
Universidade de São Paulo
Av. dos Bandeirantes, 3900, Vila
Monte Alegre
Campus USP-FFCLRP
Ribeirão Preto, São Paulo, 14040-901,
Brazil
[email protected]
João Tedim
University of Aveiro
CICECO, Ceramics and Glass
Engineering
Campus Universitário de Santiago
3810-193 Aveiro, Portugal
[email protected]
Elena Tervoort
ETH Zurich
Wolfgang-Pauli-Strasse 10, HCI G539
CH-8093 Zurich, Switzerland
[email protected]
John Texter
Eastern Michigan University
430 W. Forest Avenue
Ypsilanti, MI 48197, USA
[email protected]
94
Benjamin Thierry
Ian Wark Research Institute
University of South Australia
Mawson Lakes, SA, 5095, Australia
[email protected]
Judit Toth
University of Pannonia
Egyetem str 10
H8200 Veszprém, Hungary
[email protected]
Albert van Nierop
Distrilab Particle Technology
Olmenlaan 6C
3833 AV Leusden, The Netherlands
[email protected]
Alex M. van Herk
Eindhoven University of Technology
Polymer Chemistry
Den Dolech 2 , PO Box 513
5600MB, Eindhoven, The Netherlands
[email protected]
Maria Eugenia Velazquez-Sanchez
Parcar Desarrollos y Servicios SA de
CV
Centro de Investigación en Polímeros
Blvd Manuel Avila Camacho No. 138
PH 1 y 2, Lomas de Chapultepec
Deleg. Miguel Hidalgo, Distrito Federal
11710, Mexico
[email protected]
A.W.P. (Ronald) Vermeer
Bayer Cropscience
Alfred Nobelstrasse 50
40789 Monheim am Rhein,Germany
[email protected]
Ronald J. Veršič
Ronald T. Dodge Co.
55 Westpark Road
Dayton, Ohio 45459, USA
[email protected]
Doris Vollmer
Max Planck Institute for Polymer
Research
Ackermannweg 10
55128 Mainz, Germany
[email protected]
Dennis Vriezema
Encapson BV
Toernooiveld 1
6525 ED Nijmegen, The Netherlands
[email protected]
Mathias Walther
Pfizer Group Ltd
Ramsgate Road
Sandwich, Kent, CT13 9NJ, United
Kingdom
[email protected]
Weimin Wang
Merck & Co, Inc
770 Sumneytown Pike, WP14-3
West Point, PA 19486, USA
[email protected]
Yanhong Wen
Pharmaceutics and Analytical
Chemistry
Faculty of Pharmaceutical Science
2100 Copenhagen, Denmark
[email protected]
Gulden Yilmaz
Wageningen UR
Agrotechnology & Food Innovations
BV
Bornsesteeg 59
6708 PD Wageningen, The
Netherlands
[email protected]
Ales Zadrazil
Technicka 5
[email protected]
Sulin Zhang
Pennsylvania State University
212 EES Building
[email protected]
Vivian Mei-Sheng Lo Chou
Chou)
Newark, Delaware, USA
(Tsu-Wei
Zhanlan You (Honghao Sun)
Roskilde, Denmark
Valérie Winckler-Desprez
Roche Diagnostics GmbH
Sandhofer Strasse 116
68305 Mannheim, Germany
[email protected]
Renliang Xu
11800 SW 147 Avenue
Miami, FL 33196, USA
[email protected]
95
Notes
96
Notes
97
Notes
98
Notes
99
Notes
100
Notes
101
Receipt
This receipt acknowledges payment of _______________________
from __________________________________________________
by ____________________________________________________
for the conference registration fee for Particles 2009 held 11-14 July
2009 at the Holiday Inn Berlin – City West, Berlin, Germany.
_______________________________________
On behalf of:
265 Clover Street
Rochester, NY 14610-2246
USA
EIN No. 16-1565388
Tel: 1-585-288-5913
Fax: 1-585-482-7795
102

Particles 2009 - nanoparticles.org

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