马纳维诺凝胶作为候选杀微生物剂的生物学活性和稳定性体外评价

Efficacy and stability of maraviroc gel as a microbicide candidate in vitro

为了在体外评价马纳维诺凝胶的生物学活性和稳定性,用TZM-bl和Jurkat-T细胞系检测马纳维诺与0.015%羟乙基纤维素(HEC)复合而成的凝胶制剂的细胞毒性,对其抑制人类免疫缺陷病毒(HIV)SVPB16和SVPC12亚型假病毒感染的活性进行评价。同时将马纳维诺溶于1.5%HEC中,终浓度为6mmol/L,分别置于4℃、室温、30℃和40℃,保持相对湿度75%,每隔1周检测其抗病毒活性。结果显示,当马纳维诺与HEC复合后,其细胞毒性并没有增加,而抗病毒活性轻微增强。马纳维诺凝胶置于上述4个温度,持续8周,在高于人体温度的40℃仍保持较好的抗病毒活性。综上所述,作为候选杀微生物剂,马纳维诺凝胶具有较好的生物学活性和稳定性。

To study the efficacy and stability of maraviroc gel in vitro , the cytotoxicity of maraviroc in phosphate buffered saline （PBS） or in 0 .015% hydroxyethyl cellulose （HEC） were evaluated in TZM-bl and Jurkat-T cells .Meanwhile ,two subtypes of human immunodeficiency virus （HIV） pseudoviruses （SVPB16 and SVPC12） were used to evaluate the anti-HIV activity in vitro ,the half maximal inhibitory concentration （IC50 ） or 90% maximal inhibitory concentration （IC90 ） of maraviroc gel were assessed . Furthermore , maraviroc was dissolved in 1 .5% HEC with a final concentration of 6 mmol/L ,and then maraviroc gel was stored at 4 ℃ ,room temperature ,30 ℃ and 40 ℃ ,respectively ,in 75% relative humidity for 1 to 8 weeks . The anti-HIV activity was tested weekly .The data showed that maraviroc gel had nearly same cytotoxicity as maraviroc in PBS .HEC did not weaken the ant-HIV activity of maraviroc .Inversely ,HEC might slightly enhance the anti-HIV efficacy of maraviroc .Maraviroc gel was stable for at least 8 weeks even at 40 ℃ .It is concluded that maraviroc gel has good efficacy and stability as a microbicide candidate .