Global Women`s Health

Bioresponsive Vaginal Drug Delivery Devices to
Improve Global Women’s Health
Giovanni M. Pauletti, Ph.D.
Associate Professor of Biopharmaceutics & Pharmacokinetics
James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH (U.S.A.)
Objectives

Global women’s health

Preventive strategies

Innovative drug delivery systems

Performance in vitro

Future opportunities
Global Women’s Health
Global Women’s Health Facts:

Tobacco use among younger women in
developing countries

HIV-AIDS pandemic is increasingly “female”

Physical and sexual violence against women

>90% of adolescent mothers live in developing
countries

Essentially all maternal deaths occur in
developing countries
Source: WHO – Department of Gender, Women and Health
Global Women’s Health
Family Planning/Family Size
HIV/AIDS
Maternal Mortality
Global Women’s Health
Regional Demand for Family Planning in Africa
100
modern
traditional
unmet needs
16%
50
28%
23%
23%
0
Western
Eastern
Middle
Southern
Regions
Source: African Population and Health Research Center
Global Women’s Health
Impact of Economics on Family Planning Use in Africa
80
60
poorest 20%
wealthiest 20%
40
20
0
Western
Eastern
Middle
Southern
Regions
D. Clifton et al. Family Planning Worldwide, 2008
Global Women’s Health
Maternal Mortality
Source: World Bank , World Development Indicators
Global Women’s Health
Global Women’s Health
• zero new infections
• zero discrimination
• zero AIDS-related deaths
Preventive Strategies
Saving Lives in the Future:

Comprehensive primary health care

Gender equality

Nutrition

Prevention of child abuse

Social & emotional development

Reduction in risky behavior
Preventive Strategies
Preventive Strategies
Preventive Strategies
Limitations:




use of applicator
temperaturedependent viscosity
microbial safety
distribution
Katz et al., Drug Deliv. Transl. Res. (2011)
Innovative Drug Delivery Systems
Objective

Development of an innovative preventive/therapeutic device
that meets unique needs of women in underserved African
regions:
 self-administration without applicator
 low-cost
 socially acceptable
 rapid effectiveness
 safe
 mucoadhesive
 biodegradable
Innovative Drug Delivery Systems
Acidic Buffer Capacity
Olmsted et al., Fert. Ster. (2000)
Connor, Acquir. Immune Defic. Syndr. (2006)
Innovative Drug Delivery Systems
Bioresponsive Viscosity
Jay et al., Adv. Funct. Mater. (2009)
Innovative Drug Delivery Systems
Diffusion Coefficient [m2/s]
Bioresponsive Viscosity
0.08
HIV
100 nm LP
0.06
0.04
0.02
0.00
pH 4.3
pH 4.5
pH 4.8
Jay et al., Adv. Funct. Mater. (2009)
Innovative Drug Delivery Systems
Sol – Gel – Xerogel

solid dosage form

light-weight

biocompatible &
biodegradable materials
Supercritical
Drying
Solvent
Evaporation

chemical stability

engineered device properties
Innovative Drug Delivery Systems
Carbopol® 974P
Viscosity [cP]
410 0 5
310 0 5
2%CP/4%HPMC
Gynol II
210 0 5
110 0 5
0
3.6 3.9 4.2 4.4 4.5 4.8 5 5.2 6 6.2
Hydroxypropyl methylcellulose
Innovative Drug Delivery Systems
Tampon-like Xerogel Device
o.b.® tampon
Porosity [%]
54.1
1.9
83.0
2.9
Compression Force [N]
13.2
1.8
11.8
1.1
Hydration Rate [mg/s cm2]
3.5
0.1
13.8
0.7
Innovative Drug Delivery Systems
Tampon-like Xerogel Device
Gynol II
3% mannitol
Innovative Drug Delivery Systems
Tampon-like Xerogel Device
Engineered Properties:
5% trehalose
3% mannitol

porosity (20-90%)

hydration rate (1-15 mg/s cm2)

Compression force (5-60 N)
Innovative Drug Delivery Systems
Effect of Pore-forming Agent:
Viscosity [cP]
510 0 5
410
2%CP/4%HPMC
05
3% Mannitol
310 0 5
210 0 5
110 0 5
0
3.3
3.6
3.8
3.9
4.2
4.3
4.4
4.5
4.8
5
Innovative Drug Delivery Systems
Spreadability Work [Nxs]
Partial Rehydration of Tampon-like Xerogel Device
15
gel
xerogel
10
5
0
2% CP/5% HPMC
3% mannitol
Gynol II
Innovative Drug Delivery Systems
Spreadability Work [Nxs]
Partial Rehydration of Tampon-like Xerogel Device
6
2%CP/4%HPMC
3% Mannitol
Gynol II
4
2
0
0.5
1.0
2.0
Seminal Fluid Simulant [mL]
3.0
Innovative Drug Delivery Systems
Partial Rehydration of Tampon-like Xerogel Device
2%CP/4%HPMC
3% Mannitol
3% Trehalose
Gynol II
2
1
5
Bioadhesion Work [Nxmm]
Bioadhesion Work [Nxmm]
3
gel
xerogel
4
3
2
1
0
2% CP/5% HPMC
0
0
1
2
Time [min]
3
3% mannitol
Gynol II
Future Directions
Clinical Development of Tampon-like Xerogels:
• in vitro testing methods (efficacy/safety)
• women’s acceptability/perception
• in vivo safety/efficacy
• scale-up/production
• pharmacokinetics of medicated xerogels
• regulatory path
Acknowledgments
University of Cincinnati
Other Collaborators
• Dr. Ambikaipakan Balasubramaniam
• Dr. Saleem S. Basha
• Hua Li
• Ankit Mehta
• Dr. Sarah Potter
• Dr. Donglu Shi
• Dr. Andrew Steckl
• Shruthi Vaidhanathan
• Dr. Liaohai Chen
• Dr. Isabella Ellinger
• Dr. Yongyong Li
• Dr. James Liu
Financial Support
• Bill & Melinda Gates Foundation
• DAMD17-00-1-0202
• NIH (GM-67639; HD-048512)
• PhRMA
• UC Research Council
• UC Institute for Nanoscale Science & Technology