Box-Behnken设计法优化奥沙利铂脂质体的处方工艺

Optimization of Oxaliplatin Liposome Formulation by Box-Behnken Experimental Design

目的采用Box-Behnken实验设计法优化奥沙利铂(oxaliplatin,Ox)脂质体的制备工艺。方法以磷脂质量浓度(X1)、磷脂与Ox质量比(X2)和磷脂与胆固醇质量比(X3)为考察对象,以包封率(Y)为评价指标,采用三因素三水平的Box-Behnken实验设计筛选奥沙利铂脂质体最佳的处方。结果最优处方是磷脂质量浓度为10.20 g·L-1,磷脂与药物的质量比为31∶1,脂质体膜材料中磷脂与胆固醇质量比为3.8∶1。包封率的预测值与理论值偏差较小。结论 Box-Behnken实验设计法可用于奥沙利铂脂质体的处方优化。

OBJECTIVE To apply the Box-Behnken experimental design to optimize the formulation of oxaliplatin liposome. METHODS The independent variables were investigated by using a three-factor, three-level Box-Behnken experimental design with the concentration of phospholipid（X1）, the mass ratio of phospholipids and Ox（X2） and the mass ratio of phospholipid and cholesterol（X3） as the research object and the response variable was encapsulation efficiency. RESULTS The optimized formulation was as follows： the concentration of phospholipid is 10.20 g·L^-1, the mass ratio of phospholipid and drug was 31 ： 1 and the mass ratio of phospholipid and cholesterol was 3.8 ： 1. The deviation between the predicted values of entrapment efficiency and its theoretical values were small. CONCLUSION The Box-Behnken experimental design method can be used to optimize the formulation of oxaliplatin liposome.