Abstract 951 Poster Session IV, Tuesday, 5/4 (poster 141)

Active ingredients in currently marketed vaginal contraceptive and antimicrobial formations are detergents which are spermicidal and microbicidal. However, detergents are cytotoxic in vitro and potentially toxic to the human genital tract. Novel agents with a different spectrum of antimicrobial activity are clearly needed to protect women and newborns from sexually transmitted diseases. One candidate compound is polystyrene sulfonate (PSS) which is being developed jointly by the Program for the Topical Development of Conception and Disease, Rush University, and Advanced Care Products as a novel non-spermicidal contraceptive. In this development, we evaluated the antimicrobial activity of PSS using model culture systems. We found that PSS is highly effective against all pathogens assayed as shown in the table (ED50 is the dose of PSS needed to inhibit 50% of infection and is calculated from dose response curves).

Table 1 No caption
Full size table

Moreover, PSS exhibits little or no cytotoxicity for primary human cervical cells even at high concentrations (> 1 mg/ml). We hypothesized that PSS might block microbial adherence. Focusing on HSV, we compared the antiviral activity of PSS to heparin, a known competitive inhibitor of HSV binding. HSV binding is mediated by interactions of viral envelope glycoproteins C and/or B to cell surface heparan sulfate. We found that PSS (and heparin) completely inhibited the binding of HSV and purified soluble glycoprotein C to cells. However, PSS, but not heparin, also inhibited post-binding steps of viral entry and cell-to-cell spread of infectious virus. Notably, PSS, but not heparin, was also virucidal at concentrations > 10 µg/ml. Similarly, PSS directly kills N. gonorrhoae. The mechanism(s) of PSS microbicidal activity has yet to be determined. Additionally, in a mouse genital herpes model, a 5% PSS gel protected 15/16 mice from vaginal herpes compared with 2/16 mice treated with a placebo gel (p < 0.001). We conclude that PSS is an excellent non-cytotoxic candidate topical antimicrobial. Phase I trials are being planned.

Funded, in part, by the CONRAD program, Advanced Care Products (New Brunswick, NJ), and NIAID