星点设计-效应面法优化转铁蛋白修饰粉防己碱与硫酸长春新碱脂质体的处方

Formulation Optimization of Transferrin Modified Tetrandrine and Vincristine Liposomes by Central Composite Design-response Surface Method

目的:制备转铁蛋白(TF)修饰粉防己碱(TET)与硫酸长春新碱(VCR)的主动靶向脂质体,优化其处方。方法:以硫酸铵梯度法制备TF修饰TET与VCR脂质体,以TET包封率、VCR包封率的综合评分为指标,用星点设计-效应面法优化卵磷脂/胆固醇(EPC/Chol)摩尔比、卵磷脂/聚乙二醇2000-二硬脂酰磷脂酰乙醇胺(EPC/PEG2000-DSPE)摩尔比、TF质量分数,并进行验证试验。结果:最优处方为EPC/Chol摩尔比1.5∶1,EPC/PEG2000-DSPE摩尔比20∶1,TF质量分数0.10%;所得脂质体TET包封率为97.80%,VCR包封率为93.00%,综合评分为94.44(n=3),与其预测值93.81接近。结论:优化所得处方稳定,可用于制备TF修饰TET与VCR脂质体。

OBJECTIVE：To prepare transferrin（TF）modified tetrandrine（TET）and vincristine（VCR）active targeting liposomes,and to optimize its formulation. METHODS：TF modified TET and VCR liposomes were prepared by ammonium sulfate gradient method. Using comprehensive score of encapsulation efficiency of TET and VCR as index,central composite design-response surface method was used to optimize and validate mole ratio of EPC/Chol,mole ratio of EPC/PEG2000-DSPE and TF mass fraction. RESULTS：The optimal formulation was that the mole ratios of EPC/Chol and EPC/PEG2000-DSPE were 1.5 ∶ 1 and 20 ∶ 1,TF mass fraction was 0.10%. The encapsulation efficiency of TET and VCR were 97.80% and 93.00%,respectively. The comprehensive score was 94.44（n=3）which was close to the predicted value of 93.81. CONCLUSIONS：The optimal formulation is stable and can be used for the preparation of TF modified TET and VCR liposomes.