The success of any topical microbicide resides in the active ingredient(s), the formulation, and the deployment of that formulation. In Project 2, we will: (1) apply in vitro experimental and theoretical methods for relating formulation properties to characteristics of deployment and delivery; (2) obtain direct in vivo data for test formulations on deployment and delivery characteristics in the human vagina, under biologically important and biophysically incisive conditions; (3) elucidate linkages between new, critical in vivo deployment and delivery data and new methods for predicting them in vitro; (4) relate these data to direct measurements of the potential toxicity of test formulations in the lower and upper human female reproductive tract; and (5) use this information to rationally develop CV-N and combination formulations that are optimal in proposed deployment and delivery functions. Based on the above in vivo and in vitro studies, we anticipate that we will be able to rank the gels by their distribution based on extent of spread, tolerability and preference of the women who used them. In the in vitro testing we will quantitate and rank the gels by their biophysical characteristics. The decision as to which formulation of cyanovirin to proceed with will be based on: (1) degree of coverage of the vaginal mucosal surface; (2) substantivity of the formulation at times up to 6 hrs post insertion; (3) ability to release active drug; (4) anti-HIV activity of selected formulations; and (5) safety and acceptability of product.
