Effects of Physiological Fluids on Physical-Chemical Characteristics and Activity of Topical Vaginal Microbicide Products

The increased incidence of HIV infection in women has identified a need to develop a female controlled method to prevent sexually transmitted infections (STIs), including HIV. Formulations have been developed in our laboratory for two potential microbicide drug substances, 3-O-octyl-sn-glycerol (3-OG) and UC-781. A major concern for microbicide product development is dilution by vaginal fluids following application thereby reducing antimicrobial activity. We investigated the effect of product dilution on microbicidal activity and the product's chemical and physical properties by using vaginal fluid (VFS) and cervical mucus simulants (CMS). 3-OG and UC-781 were individually formulated into three semi-solid drug containing products: Hydroxyethylcellulose, Methylcellulose/Carbopol, and Liposome. Viscosity, osmolality, pH and in vitro activity against HIV-1 were evaluated. Results showed that pH was not affected when products were diluted with VFS; however, increases in pH were observed following CMS dilution. Viscosity was significantly decreased for all the dilutions tested excepted for some of the liposome products. Hydrogel products maintained greater activity against HIV-1 than Liposome products. The effect of dilution on anti-HIV activity varied based upon excipient choice and chemical characteristics of the active agent. These in vitro assessments can identify the potential for changes in product's physical-chemical characteristics in vivo which may result in diminished product performance.