Vaginal deployment and tenofovir delivery by microbicide gels

摘要: Gels are one of the soft material platforms being evaluated to deliver topically acting anti-HIV drugs (microbicides) vaginal environment. For each drug, its loaded concentration, gel properties and applied volume, frequency dosing can be designed optimize PK and, thence, PD. These factors also impact user sensory perceptions acceptability. Deterministic compartmental modeling deployment drug delivery achieved by test gels help delineate how multiple parameters characterizing vehicle, environment, govern details PD leakage from canal. Such microbicide is a transport process combining convection, e.g., spreading along canal, with diffusion in compartments, including gel, mucosal epithelium, stroma. The present work builds upon prior models coating flows (without convection) It combines extends these initial approaches several key ways, including: (1) linking convective due (2) accounting for natural variations dimensions canal site placement therein. Results obtained leading tenofovir, delivered three prototype gels, range rheological properties. model includes phosphorylation tenofovir diphosphate (which manifests reverse transcriptase activity host cells), stromal concentration distributions which related reference prophylactic values against HIV. This yields computed summary measure protection (“percent protected”). Analyses illustrate tradeoffs amongst properties, loading, volume placement, dimensions, time space history distribution sites action concentrations potential actions