抗HIV药物胆固醇基磷酰齐多夫定自组装体的体外药效学评价

In vitro pharmacodynamic evaluation of anti-HIV cholesteryl-phosphoryl zidovudine self-assemblies

目的考察胆固醇基磷酰齐多夫定(CPZ)自组装体的体外抗人免疫缺陷病毒(HIV)作用,为其治疗艾滋病提供实验依据。方法制备CPZ自组装体,以HIV-1感染的MT4细胞为实验模型,以合胞体产生为评价指标,与原药齐多夫定(AZT)比较,考察CPZ自组装体的抗HIV作用。同时采用MTT法考察CPZ自组装体的细胞毒性。考察了RAW264.7细胞对CPZ自组装体的吞噬作用。结果 CPZ自组装体的抗HIV活性与AZT比较大大增强,其半数有效浓度(EC50)是AZT的1/10～1/50,选择系数较大,安全性高。结论 CPZ自组装体的抗HIV作用较强,有望成为治疗艾滋病新药。

Objective To evaluate the anti-HIV activity of the self-assemblies of cholesteryl-phosphoryl zidovudine（CPZ） and provide evidence for the promising new anti-HIV drug.Methods CPZ self-assemblies were prepared.The MT4 cells infected by HIV-1 were the model to evaluate the anti-HIV activity of CPZ self-assemblies,which based on the generation of combined cells,was compared to that of the parent drug-zidovudine（AZT）.The cytotoxicity of CPZ self-assemblies as evaluated by the MTT method.Phagocytosis of macrophage to CPZ self-assemblies was evaluated in RAW264.7 cells.Results The anti-HIV activity of CPZ self-assemblies was much higher than that of AZT,with the half effective concentration（EC50） 1/10 to 1/50 that of AZT.The selectivity index（SI） was high,indicating that the self-assemblies were safe.Conclusion CPZ self-assemblies have high anti-HIV activity and is a promising anti-HIV drug.