Transport Processes in Vaginal Films that Release Anti-HIV Microbicide Molecules

Abstract

A promising method for blocking sexual transmission of HIV is application of topical microbicide molecules to mucosal surfaces and the fluids contacting them. There is widespread agreement that more effective and diverse drug delivery vehicles, as well as better active ingredients, must be developed to increase microbicide efficacy. There is now great interest in developing a variety of delivery vehicles to suit the preferences of a diverse group of users. These include intravaginal rings and dissolving films, as well as the original microbicide gels. Here, we develop a mechanistic mathematical model of the dissolution of a microbicide-bearing polymer film, and subsequent distribution of its active drug throughout the vaginal lumen. The film dissolves by first imbibing (or taking up) solvent (vaginal fluid), whereupon its material structure changes in a way that frees individual polymer molecules in the film to move. In the model, the polymer structural relaxation via water uptake forms a two-phase, glassy-rubbery system in which interfacial movement follows Fickian (i.e. diffusion dominated) dynamics. However, at some intermediate time the interfacial motion ceases to follow Fickian dynamics, due to viscoelastic stresses in the polymer. As the glassy polymer transforms into a rubbery polymer, drugs carried within the film are freed to move throughout the relaxed network, and begin to diffuse through the vaginal lumen in all directions, especially laterally between the apposed vaginal walls. Therefore, as the initially fully glassy polymer matrix relaxes to a two-phase, glassy-rubbery system, the governing diffusion equation is simultaneously solved to track the motion of released drug molecules in the vaginal lumen and model the drug delivery. This is the first mechanistic model of how a vaginal film releases microbicidal molecules to neutralize HIV virions and inhibit transmission. [Supported by NIH AI077289]