The """"""""Duet"""""""" is a cervical barrier device that, unlike a diaphragm, delivers gel on both its upper and lower surfaces to protect the vagina as well as the cervix. This application proposes 3 related projects: 1) """"""""BufferGel-Duet"""""""", a single-use product for protection against STIs, HIV/AIDS, BV, and pregnancy. (a) Complete development of manufacturing steps to produce Duet for clinical efficacy trials. (b) Complete development of packaging, stability, and shelf-life testing of BufferGel-Duet. (c) Seek FDA permission via ReProtect's BufferGel IND to pursue clinical trials of BufferGel-Duet for preventing STIs (chlamydia, gonorrhea, trichomoniasis, and HIV), BV, and for contraception. 2) Reusable Duet, a low-cost, and maximally protective barrier device for use in low resource areas. Submit IDE to FDA for Duet as an OTC cervical barrier device for use with microbicides. 3) Membrane permeant acids: Determine whether lactic and acetic acid can safely increase microbicide efficacy. Lactobacilli acidify the vagina to pH~4 by secreting lactic and acetic acids. At this pH these acids can rapidly inactivate pathogens by permeating cell and bacterial membranes, but these permeant acids can also be toxic to mucosal surfaces. We hypothesize that adding lactic and acetic acids at physiological concentrations to microbicides formulated at pH~4 will speed acid-inactivation of pathogens without causing significant toxicity. To test this hypothesis: (a) Measure in vitro the speed at which lactic acid and acetic acid at vaginal pH (~4) inactivate sexually transmitted pathogens, BV-associated microbes, and sperm, (b) Add physiological concentrations of these acids to BufferGel (which uses an impermeant buffering gel to reinforce vaginal acidity) and measure the extent to which they increase its protective efficacy in animal models for herpes, chlamydia, and trichomonas. (c) Test whether adding these acids to BufferGel increases vaginal toxicity, or susceptibility to herpes or chlamydia, by using sensitive tests in mouse and rabbit models.
The aim is to maximize protective efficacy of microbicides that women can use for protection against STIs and HIV. The products will also prevent pregnancy and help prevent BV. BufferGel is now in clinical trials for contraception (used with a diaphragm) and HIV prevention (used alone). """"""""Duet"""""""" covers the cervix for maximum protection of this susceptible site for infections, and delivers microbicide gel to protect both the cervix and vagina. The reusable Duet will be low in cost and useful for low-resource areas.
