Thermoreversible gel formulations containing sodium lauryl sulfate or n-lauroylsarcosine as potential topical microbicides against sexually transmitted diseases

The microbicidal efficacies of two anionic surfactants, sodium lauryl sulfa te (SLS) and n-lauroylsarcosine (LS), were evaluated in cultured cells and in a murine model of herpes simplex type 2 (HSV-2) intravaginal infection. In vitro studies showed that SLS and LS were potent inhibitors of the infec tivity of HSV-2 strain 333. The concentrations of SLS which inhibit viral i nfectivity by 50% (50% inhibitory dose) and 90% (90% inhibitory dose) were 32.67 and 46.53 muM, respectively, whereas the corresponding values for LS were 141.76 and 225.30 muM. In addition, intravaginal pretreatment of mice with thermoreversible gel formulations containing 2.5% SLS or 2.5% LS prior to the inoculation of HSV-2 strain 333 completely prevented the developmen t of genital herpetic lesions and the lethality associated with infection. Of prime interest, no infectious virus could be detected in mouse vaginal m ucosa. Both formulations still provided significant protection when viral c hallenge was delayed until 1 h after pretreatment. Finally, intravaginal ap plication of gel formulations containing 2.5% SLS or 2.5% LS once daily for 14 days to rabbits did not induce significant irritations to the genital m ucosa, as demonstrated from macroscopic and histopathologic examinations. T hese results suggest that thermoreversible gel formulations containing SLS or LS could represent potent and safe topical microbicides for the preventi on of HSV-2 and possibly other sexually transmitted pathogens, including hu man immunodeficiency virus.