Cellulose acetate phthalate (CAP): an 'inactive' pharmaceutical excipient with antiviral activity in the mouse model of genital herpesvirus infection

The spread of sexually transmitted infections caused by herpes simplex viru s type 2 (HSV-2) has continued unabated. At least 20% of the United States population has been infected with HSV-2 and there is a high probability of further virus transmission by asymptomatic carriers. Given the absence of e ffective vaccines, this indicates the need to develop prophylactic measures such as topical microbicides that have antiviral Recent studies indicate t hat cellulose acetate phthalate (CAP), an inactive pharmaceutical excipient commonly used in the production of enteric tablets and capsules, is a broa d specificity microbicide against diverse sexually transmitted pathogens. W hen appropriately formulated in micronized form, it inactivates various vir uses, including HSV-2, in vitro. Here we show that CAP inhibits HSV-2 infec tion in the mouse model of genital HSV-2 infection. Pretreatment with micro nized CAP formulated in a glycerol-based cream with colloidal silicone diox ide significantly reduced the proportion of HSV-2-infected mice (10% virus shedding, 0-5% lesion development and 0% fatality for CAP as compared to 84 % shedding, 63% lesion development and 63% fatality in saline-treated mice) . These differences were significant (P less than or equal to 0.0002 by the test of equality of two proportions). Virus titres in the minority of mice that developed infection were similar to those in untreated mice. HSV-2 in fection was not inhibited by treatment with CAP formulated with other inact ive ingredients (for example povidone plus crosprovidone) instead of silico ne dioxide, presumably reflecting CAP complexation/inactivation. These data suggest that properly formulated, CAP may be an efficacious agent for prev enting vaginal transmission of genital herpesvirus infections.