SAFETY TESTING OF SILICONE ELASTOMER MATRIX VAGINAL RINGS CONTAINING UC781 AND TWEEN 80 USING EPIVAGINAL(VEC-606) TISSUES.

• TR Number: 577
• Keywords: EpiVaginal (VEC-606), GM-CSF, IFNg, IL-10, IL-12, IL-17, IL-1a, IL-1b, IL-2, IL-4, IL-6, IL-8, Microbial agent, Tissue viability, TNF-a, Transepithelial electrical resistance (TEER), Vaginal rings

The microbicidal agent UC781 has very limited aqueous solubility. A recent study in pig-tailed macaques showed poor pharmacokinetic levels, suggesting that, unlike in vitro release testing which uses relatively large volumes of a hydroalcoholic release media, the vaginal environment does not provide equivalent solubilising power to dissolve UC781 diffused from the ring. To overcome this solubility obstacle, the non-ionic surfactant Tween 80 was co-formulated with UC781 in silicone elastomer rings. However, given the phase 2/3 trial results testing vaginal use of nonoxynol-9 as a candidate microbicide showed an increased HIV infection risk due to disruptions in the vaginal epithelium, the use of surfactants in microbicide vaginal rings requires safety evaluation early in the formulation development phase. This study reports in vitro release of UC781 rings with and without the addition of Tween 80 into simulated vaginal fluid (SVF), and safety testing of the rings using the EpiVaginal tissue model.