Microbicide Efficacy and Toxicity Tests in a Mouse Model for Vaginal Transmission of Chlamydia trachomatis

Abstract

Microbicides are being developed for woman-controlled protection against sexually transmitted diseases (STDs). The goal of the study was to test candidate microbicides in a mouse model for preventing vaginal transmission of and for acute toxicity to columnar epithelium. Progestin-sensitized CF-1 mice were treated vaginally with 50 microl of microbicide, followed either by vaginal inoculation with 10 ID(50) of serovar D or by examination of the epithelial surface for acute toxicity with a viability stain (ethidium homodimer-1). Nonoxynol-9 (N9), sodium dodecyl sulfate (SDS), chlorhexidine digluconate, and BufferGel all provided significant though incomplete protection against vaginal transmission. Other candidates, all of which were effective in vitro, provided no vaginal protection: kappa-carrageenan, dextran sulfate, polystyrene sulfonate, Concanavalin A, wheat germ agglutinin, and agglutinin. The surface-active agents (N9, SDS, and chlorhexidine) caused significant acute epithelial toxicity: 3 days after chlorhexidine exposure, mice also had vaginal friability and markedly increased susceptibility to. BufferGel was the only candidate tested that was both protective and relatively nontoxic. Microbicides can provide vaginal protection against in highly susceptible progestin-sensitized mice. Since N9 does not inactivate, it likely protects by killing target cells in the vagina. Despite the ability to both potently inactivate and kill target cells, two surface-active agents, SDS and chlorhexidine, failed to provide complete protection, a circumstance which emphasizes the importance of distributing microbicides to all susceptible surfaces.