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

关键词:  奥沙利铂  脂质体  包封率  Box-Behnken实验设计

Key words:  oxaliplatin  liposome  entrapment efficiency  Box-Behnken experimental design

摘要:

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。

Abstract:

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.