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  • Title: Microbicide efficacy and toxicity tests in a mouse model for vaginal transmission of Chlamydia trachomatis.
    Author: Achilles SL, Shete PB, Whaley KJ, Moench TR, Cone RA.
    Journal: Sex Transm Dis; 2002 Nov; 29(11):655-64. PubMed ID: 12438901.
    Abstract:
    BACKGROUND: Microbicides are being developed for woman-controlled protection against sexually transmitted diseases (STDs). GOAL: 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. STUDY DESIGN: 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). RESULTS: 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. CONCLUSION: 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.
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