Composite films for vaginal delivery of tenofovir disoproxil fumarate and emtricitabine

Prevention of male-to-female HIV transmission remains a huge challenge and topical pre-exposure prophylaxis (PrEP) using microbicides may help overcoming the problem. In this work, different types of films containing the antiretroviral drugs tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) were developed. Formulations based in poly(vinyl alcohol) and pectin were produced as single- or double-layered films. Films containing TDF/FTC or TDF/FTC-loaded Eudragita (R) L 100 nanoparticles (NPs) obtained by nano spray-drying were tested for physicochemical, technological and biological properties relevant to microbicide development. All systems featured organoleptic and mechanical properties considered suitable for vaginal use and potentially favoring users' acceptability. Film design (single- or double-layered, and the incorporation or not of NPs) had a greater impact on disintegration time and drug release in a simulated vaginal fluid. Upon film disintegration, pH and osmolality of the fluid remained within values considered compatible with the vaginal environment. Double-layered films significantly reduced burst effect and the overall release of both drugs as compared to fast releasing, single-layered films. The effect on delaying drug release was most noticeable when TDF/FTC-loaded NPs were incorporated into double-layered films. This last design seems particularly advantageous for the development of a coitus-independent, on-demand microbicide product. Moreover, all film types were shown potentially safe when evaluated by the MTT metabolic activity and lactate dehydrogenase release assays using HeLa and CaSki cervical cell lines. Overall, results support that proposed films may be suitable for the vaginal delivery of TDF/FTC in the context of topical PrEP.