UC-781

The Woman's Condom is a new female condom that uses a dissolvable polyvinyl alcohol capsule to simplify vaginal insertion. This preclinical study assessed the feasibility to incorporate an antiviral drug, UC781, into the Woman's Condom capsule, offering a unique drug delivery platform.

UC781 capsules were fabricated using methods from the development of the Woman's Condom capsules as well as those used in vaginal film development. Capsules were characterized to evaluate physical/chemical attributes, Lactobacillus compatibility, in vitro safety and bioactivity, and condom compatibility.

Two UC781 capsule platforms were assessed. Capsule masses (mg; mean±SD) for platforms 1 and 2 were 116.50±18.22 and 93.80±8.49, respectively. Thicknesses were 0.0034±0.0004 in and 0.0033±0.0004 in. Disintegration times were 11±3 s and 5±1 s. Puncture strengths were 21.72±3.30 N and 4.02±0.83 N. Water content measured 6.98±1.17% and 7.04±1.92%. UC781 content was 0.59±0.05 mg and 0.77±0.11 mg. Both platforms retained in vitro bioactivity and were nontoxic to TZM-bl cells and Lactobacillus. Short-term storage of UC781 capsules with the Woman's Condom pouch did not decrease condom mechanical integrity.

UC781 was loaded into a polymeric capsule similar to that of the Woman's Condom product. This study highlights the potential use of the Woman's Condom as a platform for vaginal delivery of drugs relevant to sexual/reproductive health, including those for short- or long-acting HIV prevention.

We determined the proof-of-concept feasibility of incorporation of an HIV-preventative microbicide into the Woman's Condom capsule. This study highlights various in vitro physical and chemical evaluations as well as bioactivity and safety assessments necessary for vaginal product development related to female sexual and reproductive health.

This study describes the preclinical development of a matrix-type silicone elastomer vaginal ring device designed to provide controlled release of UC781, a non-nucleoside reverse transcriptase inhibitor. Testing of both human- and macaque-sized rings in a sink condition in vitro release model demonstrated continuous UC781 release in quantities considered sufficient to maintain vaginal fluid concentrations at levels 82-860-fold higher than the in vitro IC50 (2.0 to 10.4 nM) and therefore potentially protect against mucosal transmission of HIV. The 100-mg UC781 rings were well tolerated in pig-tailed macaques, did not induce local inflammation as determined by cytokine analysis and maintained median concentrations in vaginal fluids of UC781 in the range of 0.27 to 5.18 mM during the course of the 28-day study. Analysis of residual UC781 content in rings after completion of both the in vitro release and macaque pharmacokinetic studies revealed that 57 and 5 mg of UC781 was released, respectively. The pharmacokinetic analysis of a 100-mg UC781 vaginal ring in pig-tailed macaques showed poor in vivo-in vitro correlation, attributed to the very poor solubility of UC781 in vaginal fluid and resulting in a dissolution-controlled drug release mechanism rather than the expected diffusion-controlled mechanism.