Efficacies of Topical Formulations of Foscarnet and Acyclovir and of 5-Percent Acyclovir Ointment (Zovirax) in a Murine Model of Cutaneous Herpes Simplex Virus Type 1 Infection

Abstract

The topical efficacies of foscarnet and acyclovir incorporated into a polyoxypropylene-polyoxyethylene polymer were evaluated and compared to that of 5% acyclovir ointment (Zovirax) by use of a murine model of cutaneous herpes simplex virus type 1 infection. All three treatments given three times daily for 4 days and initiated 24 h after infection prevented the development of the zosteriform rash in mice. The acyclovir formulation and the acyclovir ointment reduced the virus titers below detectable levels in skin samples from the majority of mice, whereas the foscarnet formulation has less of an antiviral effect. Reducing the number of treatments to a single application given 24 h postinfection resulted in a significantly higher efficacy of the formulation of acyclovir than of the acyclovir ointment. Acyclovir incorporated within the polymer was also significantly more effective than the acyclovir ointment when treatment was initiated on day 5 postinfection. The higher efficacy of the acyclovir formulation than of the acyclovir ointment is attributed to the semiviscous character of the polymer, which allows better penetration of the drug into the skin.

Development of Novel Microemulsion-Based Topical Formulations of Acyclovir for the Treatment of Cutaneous Herpetic Infections

“…This can be explained as when the virus is inoculated in the skin, where the primary infection occurs; it starts spreading from this site, probably by retrograde axonal flow, to sensory ganglia and the central nervous system. Thereafter, the virus reaches axons that innervate skin within the same dermatome as the inoculation site, spreads via orthograde flow into the skin, and produces herpetic lesions within the affected dermatome (10). On the sixth day, herpetic skin lesions appeared in the form of small vesicles distant from inoculation site.…”

“…Murine model of cutaneous HSV-I infection was used to study the antiviral effect of ACV microemulsion. HSV-I propagated in Vero cells (African green monkey kidney cells) in minimum essential medium and female BALB/c mice (5-7 weeks old) were used in this study (10). The plaque assay was performed to check the viral infectivity (11).…”

“…Animals were anesthetized by intraperitoneal injection of a mixture containing 70 mg of ketamine hydrochloride and 11.5 mg of xylazine per kilogram of body weight. Mice were then cutaneously infected with HSV-1 after scarification (scratching the skin six times in a crossed-hatched pattern) of the shaved right mid-flank region with a 27-gauze needle held vertically (10,12). Treatment was initiated 24 h post-infection (i.e.…”

Efficacies of Gel Formulations Containing Foscarnet, Alone or Combined with Sodium Lauryl Sulfate, against Establishment and Reactivation of Latent Herpes Simplex Virus Type 1

“…Conversely, the inoculation of HSV-1 strain F in the lumbosacral area of hairless mice (zosteriform model) was associated with an approximately 50 to 60% mortality rate among untreated infected mice (26,27). The efficacies of gel formulations containing foscarnet, alone or in combination with SLS, given 6 or 24 h after virus inoculation reduced to a similar extent the development of herpetic orofacial lesions.…”

“…Previous studies from our laboratory have demonstrated that the efficacy of 5% acyclovir incorporated into a polymer composed of polyoxyethylene and polyoxypropylene was better than that of the commercial acyclovir ointment (Zovirax) in reducing the development of herpetic skin lesions in mice after a single application 24 h postinfection (27). The improved efficacy of the gel formulation of acyclovir was attributed to the semiviscous character of the polymer, which allows a more efficient drug penetration into the skin.…”