Sodium Lauryl Sulfate Increases the Efficacy of a Topical Formulation of Foscarnet against Herpes Simplex Virus Type 1 Cutaneous Lesions in Mice

The influence of sodium lauryl sulfate (SLS) on the efficacies of topical gel formulations of foscarnet against herpes simplex virus type 1 (HSV-1) cutaneous infection has been evaluated in mice. A single application of the gel formulation containing 3% foscarnet given 24 h postinfection exerted only a modest effect on the development of herpetic skin lesions. Of prime interest, the addition of 5% SLS to this gel formulation markedly reduced the mean lesion score. The improved efficacy of the foscarnet formulation containing SLS could be attributed to an increased penetration of the antiviral agent into the epidermis. In vitro, SLS decreased in a concentration-dependent manner the infectivities of herpesviruses for Vero cells. SLS also inhibited the HSV-1 strain F-induced cytopathic effect. Combinations of foscarnet and SLS resulted in subsynergistic to subantagonistic effects, depending on the concentration used. Foscarnet in phosphate-buffered saline decreased in a dose-dependent manner the viability of cultured human skin fibroblasts. This toxic effect was markedly decreased when foscarnet was incorporated into the polymer matrix. The presence of SLS in the gel formulations did not alter the viabilities of these cells. The use of gel formulations containing foscarnet and SLS could represent an attractive approach to the treatment of herpetic mucocutaneous lesions, especially those caused by acyclovir-resistant strains.

本研究在小鼠模型中评估了十二烷基硫酸钠（sodium lauryl sulfate, SLS）对膦甲酸钠外用凝胶制剂抗1型单纯疱疹病毒（herpes simplex virus type 1, HSV-1）皮肤感染的药效影响。于感染后24小时单次涂抹含3%膦甲酸钠的凝胶制剂，仅对疱疹性皮肤病变的进展产生轻度抑制效果。最为关键的发现是，在该凝胶制剂中添加5%的十二烷基硫酸钠后，平均病变评分显著降低。含十二烷基硫酸钠的膦甲酸钠制剂药效得以提升，这可归因于抗病毒药物向表皮的渗透能力增强。体外实验结果显示，十二烷基硫酸钠以浓度依赖性方式降低疱疹病毒对Vero细胞（Vero cells）的感染性。此外，十二烷基硫酸钠还可抑制HSV-1 F毒株诱导的细胞病变效应。膦甲酸钠与十二烷基硫酸钠联用的效应依所用浓度不同，呈现亚协同至亚拮抗的变化。磷酸盐缓冲液（phosphate-buffered saline, PBS）中的膦甲酸钠，可呈剂量依赖性降低体外培养的人皮肤成纤维细胞的存活率。当膦甲酸钠被嵌入聚合物基质后，该毒性作用显著减弱。凝胶制剂中添加十二烷基硫酸钠，并不会改变这些细胞的存活率。包含膦甲酸钠与十二烷基硫酸钠的外用凝胶制剂，有望成为治疗疱疹性黏膜皮肤病变的极具前景的手段，尤其是针对阿昔洛韦耐药毒株引发的病变。