共递送柔红霉素与高三尖杉酯碱的叶酸修饰脂质体的制备与质量评价

Preparation and quality evaluation of folic acid modified daunorubicin and homohar⁃ringtonine co-delivery liposomes

目的评估柔红霉素(DNR)与高三尖杉酯碱(HHT)联合用药对HL60细胞增殖的抑制作用;制备叶酸修饰的共递送DNR+HHT的复合脂质体。方法采用MTT法检测细胞增殖,CompuSyn软件计算DNR与HHT的联合用药指数。以薄膜水化法制备脂质体,在单因素试验基础上,采用Box-Behnken响应面法优化共递送脂质体的处方;通过正交试验设计优化制备工艺。结果DNR+HHT的联合用药指数为0.69,两者具有协同作用。优选处方为:磷脂10.7μmol·mL^(-1),磷脂-胆固醇的摩尔比为4:1,磷脂-DNR的用量比为15:1。优选制备工艺为:水合时间2 h,水合温度40℃,油水比例为2:1。结论Box-Behnken响应面法结合正交试验设计可有效优化共递送脂质体的处方与制备工艺,所得脂质体的包封率高、粒度均匀。

OBJECTIVE To investigate the combination effect of daunorubicin(DNR)and homoharringtonine(HHT)on HL-60 cell proliferation inhibition.To prepare folic acid modified DNR and HHT co-delivery liposomes(FADHLP).METHODS HL-60 cell proliferation was measured by MTT method.The combination index of DNR and HHT was calculated by CompuSyn software.The co-delivery liposomes were prepared by thin film hydration method.On the basis of single factor test,Box-Behnken response surface methodology was used to optimize the formulation.The preparation process was optimized by Orthogonal experiment design.RESULTS The combination index of DNR and HHT was 0.69,indicating that they showed synergistic effects on inhibiting the proliferation of HL60 cells.The optimal formulation was as follows:the concentration of phospholipid was 10.71μmol·mL^(-1),the ratio of phospholipid to cholesterol was 4:1,and the ratio of phospholipid to DNR was 15:1.The optimal preparation process was follows:the ratio of oil to water was 2:1,hydration time was 2 h,and the hydration temperature was 40℃.CONCLUSION The formulation and preparation process of the FADHLP can be optimized by Box-Behnken response surface optimization method and orthogonal design test effectively.The liposomes prepared show high encapsulation efficiency and uniform particle size.