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

Abstract

The spread of sexually transmitted infections caused by herpes simplex virus 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 effective vaccines, this indicates the need to develop prophylactic measures such as topical microbicides that have antiviral activity. Recent studies indicate that cellulose acetate phthalate (CAP), an inactive pharmaceutical excipient commonly used in the production of enteric tablets and capsules, is a broad specificity microbicide against diverse sexually transmitted pathogens. When appropriately formulated in micronized form, it inactivates various viruses, including HSV-2, in vitro. Here we show that CAP inhibits HSV-2 infection in the mouse model of genital HSV-2 infection. Pretreatment with micronized CAP formulated in a glycerol-based cream with colloidal silicone dioxide 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 < or = 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 infection was not inhibited by treatment with CAP formulated with other inactive ingredients (for example povidone plus crosprovidone) instead of silicone dioxide, presumably reflecting CAP complexation/inactivation. These data suggest that properly formulated, CAP may be an efficacious agent for preventing vaginal transmission of genital herpesvirus infections.