Thermoreversible Gel Formulations Containing Sodium Lauryl Sulfate or n -Lauroylsarcosine as Potential Topical Microbicides against Sexually Transmitted Diseases

Abstract

The microbicidal efficacies of two anionic surfactants, sodium lauryl sulfate (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 infectivity of HSV-2 strain 333. The concentrations of SLS which inhibit viral infectivity by 50% (50% inhibitory dose) and 90% (90% inhibitory dose) were 32.67 and 46.53 M, respectively, whereas the corresponding values for LS were 141.76 and 225.30 M. 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 development of genital herpetic lesions and the lethality associated with infection. Of prime interest, no infectious virus could be detected in mouse vaginal mucosa. Both formulations still provided significant protection when viral challenge was delayed until 1 h after pretreatment. Finally, intravaginal application 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 mucosa, as demonstrated from macroscopic and histopathologic examinations. These results suggest that thermoreversible gel formulations containing SLS or LS could represent potent and safe topical microbicides for the prevention of HSV-2 and possibly other sexually transmitted pathogens, including human immunodeficiency virus.

A Review of Current Intravaginal Drug Delivery Approaches Employed for the Prophylaxis of HIV/AIDS and Prevention of Sexually Transmitted Infections

“…Ward and Ashley (138) were demonstrated that SLS at low concentrations is a potent inactivator of rotavirus and poliovirus. Previous in vitro studies have demonstrated the ability of SLS to inhibit the infective capacity of different enveloped viruses such as HSV-1, HSV-2, and HIV-1 (139)(140)(141). This suggested that SLS could be a candidate for use as an intravaginal microbicide gel formulation to prevent the sexual transmission of STIs and HIV (139).…”

“…Bernstein et al (146) showed that a 5% w/w Carbopol gel can be a suitable vehicle for the intravaginal administration of SPL7013 (147). SPL7013 binds and blocks HIV-1 thereby preventing STIs, including HIV and genital herpes (108,144,141). Phase I trials have shown that VivaGel™ is safe and well-tolerated.…”

Comparative Study of Mechanisms of Herpes Simplex Virus Inactivation by Sodium Lauryl Sulfate and n -Lauroylsarcosine

“…As we have previously shown (30,34), SLS is a potent inhibitor of HSV-1 strain F and HSV-2 strain 333 infectivities for Vero cells. Howett et al (15) have also reported that pretreatment of HSV-2 strain 333 with SLS at a concentration of 867 M for 10 min at 37°C completely inactivated the infectivity of the virus for CV-1 cells.…”

“…We have also demonstrated that n-lauroylsarcosine (LS), another anionic surfactant structurally close to SLS, inactivates HSV infectivity in vitro (34). Moreover, gel formulations containing SLS or LS were very effective in preventing HSV-2 infection following intravaginal challenge in mice.…”

“…Sodium lauryl sulfate (SLS), an anionic surfactant with protein denaturant potency, has been demonstrated to be a potent inhibitor of the infectivities of different strains of enveloped viruses such as HSV and HIV-1 as well as nonenveloped viruses such as papillomaviruses in vitro (4,30,34). We have also demonstrated that n-lauroylsarcosine (LS), another anionic surfactant structurally close to SLS, inactivates HSV infectivity in vitro (34).…”