In Vitro Human Tissue Model for Intravaginal Drug Delivery

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$267,914.00
Award Year:
2010
Program:
SBIR
Phase:
Phase I
Contract:
1R43GM093563-01
Agency Tracking Number:
GM093563
Solicitation Year:
n/a
Solicitation Topic Code:
NIGMS
Solicitation Number:
n/a
Small Business Information
MATTEK CORPORATION
MATTEK CORPORATION, 200 HOMER AVE, ASHLAND, MA, 01721
Hubzone Owned:
N
Socially and Economically Disadvantaged:
N
Woman Owned:
N
Duns:
147365936
Principal Investigator:
SEYOUM AYEHUNIE
(508) 881-6771
SAYEHUNIE@MATTEK.COM
Business Contact:
MITCHELL KLAUSNER
() -
mklausner@mattek.com
Research Institution:
n/a
Abstract
DESCRIPTION (provided by applicant): Due to the avoidance of first-pass hepatic metabolism and gastrointestinal irritation, intravaginal administration is an attractive option for systemic delivery of drugs. Current vaginal drug delivery studies are primar ily performed using the FDA-accepted rabbit model. However, such studies are costly and time consuming. In addition, animal experiments are often highly variable. To avoid these problems, we propose use of a highly differentiated and reproducible, in vitro reconstructed human vaginal ectocervical (VEC) tissue model such as MatTek EpiVaginalTM model. However, the barrier properties of the EpiVaginal model need to be optimized so that they accurately match those of native in vivo tissue. . Phase Iresearch wi ll produce various EpiVaginal cultures in which the tissue phenotype has been modified. These tissues will be characterized in terms of histology, barrier properties (measured by transepithelial electrical resistance), and the presence of organelles import ant in determining mucosal barrier properties such as desmosomes and tight junctions. In addition, the levels of barrier lipids will be quantified. The most promising tissues will be selected for drug permeability studies using a set of model drugs for whi ch historical pharmacokinetic intravaginal rabbit data are available. The in vitro and in vivo data will be compared to choose the tissue with optimized barrier properties. Finally, the economics of utilizing the in vitro tissue model for pre-clinical intr avaginal drug delivery studies versus rabbit studies will be compared. PUBLIC HEALTH RELEVANCE: The vaginal route has a great potential for systemic drug delivery due to its large surface area, high vascularization, permeability to a wide range of c ompounds including peptides and proteins, and avoidance of the hepatic first-pass metabolism and gastrointestinal irritation. Since drug absorption potential has become important criterion for decisions early in the drug discovery process, there is a great need to develop a reliable screening method for drug adsorption through the vaginal route. This proposal will optimize a highly differentiated, human vaginal tissue model to facilitate such studies.

* information listed above is at the time of submission.

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