Sustained release of microbicides by newly engineered vaginal rings. AIDS.

Sustained release of microbicides by newly engineered vaginal rings. AIDS.

for adherence to appropriate application of effective, nontoxic products being a major deterrent. Saxena and colleagues explored methods to enable sustained release of combinations of antiretroviral microbicides, utilizing intravaginal rings composed of biosoluble Acacia gum or non-biodegradable hydrogel of 2-hydroxyethyl methacrylate and sodium methacrylate, materials approved for use by the United States Food and Drug Administration. The reverse transcriptase inhibitors TMC120, PMPA, 3’-azido-3’-deoxythymidine, and a newly characterized anti-HIV agent, Boc-lysinated betulonic acid, were incorporated into vaginal rings with different combinations. Daily and cumulative release rates of these inhibitors in ring eluates were determined by high-performance liquid chromatography, gas chromatography, or immunoassay. Anti-HIV effects were measured by assessment of p24 Gag antigen in T-cell cultures exposed to HIV-1 isolates. Drug release rates were sustained at concentrations higher than the minimum effective dose for HIV inhibition. The release was maintained for no less than 15 and 28 days from the Acacia gum and 2-hydroxyethyl methacrylate and sodium methacrylate rings, respectively. Boc-lysinated betulonic acid showed more than 90% inhibition of HIV-1 infection in H9 cells, with little toxicity to normal cells. The intravaginal rings described here are capable of efficacious drug delivery. Incorporation of several antiretroviral agents, including betulinol derivatives, which act at multiple levels of the HIV life cycle, may provide a synergistic effect to achieve higher efficacy on the inhibition of HIV infection.

Although many participants in microbicide gel trials report the unexpected benefit of improved sexual satisfaction with gel use, work is proceeding with alternate microbicide delivery systems that have other potential advantages. Those include sustained delivery through a ring that could be put into position monthly, for example. Not having to insert a microbicide before each sex act would likely appeal to many women, particularly if the vaginal ring releases locally active, effective, and safe antiretroviral drugs for prevention.