中心组合设计-效应面法优化RGD修饰粉防己碱-异长春花碱脂质体处方

Formulation Optimization of RGD Modified TET-VRB Liposomes by Central Composite Design-Response Surface Method

目的采用中心组合设计-效应面法优选精氨酸-甘氨酸-天冬氨酸(RGD)修饰粉防己碱(TET)-异长春花碱(VRB)脂质体的最佳处方。方法采用主动载药法中的硫酸铵梯度法,制备RGD修饰TET-VRB脂质体。用高效液相色谱法(HPLC)分别测定脂质体的包封率。以卵磷脂与胆固醇的摩尔比(EPC/Chol)、卵磷脂与聚乙二醇2000-二硬脂酰磷脂酰乙醇胺的摩尔比(EPC/PEG 2000-DSPE)、EPC与VRB的质量比(EPC/VRB)3个因素作为自变量,考察各因素对包封率的影响,并对每个因素进行二项式拟合,运用效应曲面函数求出最佳处方。结果优选出的RGD修饰TET-VRB脂质体的最佳处方是EPC/Chol=1.5:1,EPC/PEG 2000-DSPE=20:1,EPC/VRB=15:1。结论中心组合设计-效应面法操作简单、准确度高、预测性好,优选出的处方制备RGD修饰TET-VRB脂质体符合设计要求。

Objective To optimize the formulation of RGD modified tetrandrine（TET）-vinorelbine（VRB） liposomes using central composite design-response surface method. Methods The RGD modified TET-VRB liposomes were prepared by ammonium sulfate gradient method, which belongs to active loading methods. The encapsulation efficiency of the liposomes was measured by HPLC. The mass ratio of egg phosphatidylcholine to vinorelbine（EPC/VRB）, the mole ratios of egg phosphatidylcholine to cholesterol（EPC/Chol） and egg phosphatidylcholine to PEG 2000-distearoyl phosphatidylethanolamine（EPC/PEG 2000-DSPE） were investigated as independent variables, and the impaction of the factors on the encapsulation efficiency were examined. Finally, each of factors was fitted using response surface function, and the optimal formulation was found. Results The optimal formulation was as follows： EPC/VRB=15：1, EPC/Chol=1.5：1, EPC/PEG 2000-DSPE=20：1. Conclusion Central composite design-response surface method was convenient to use with simple operation, high accuracy and good predictability. The prepared RGD modified TET-VRB liposomes reaches the design requirements.