星点效应面法对多西他赛他莫昔芬复方脂质体处方的优化

Formulation Optimization of Docetaxel-tamoxifen Liposomes by Central Composite Design-response Surface Method

目的:优化多西他赛他莫昔芬复方脂质体处方。方法:采用单因素试验考察脂药比、大豆磷脂/胆固醇比、枸橼酸他莫昔芬/多西他赛比3个因素对脂质体粒径、ζ电位、分散度指数(PdI)、药物包封率和载药量的影响;采用2因素5水平的星点设计-效应面法,以多西他赛包封率和载药率为评价指标进行处方优化。结果:最优处方为脂药比为19∶1,大豆磷脂/胆固醇比为9∶1,多西他赛的包封率为(82.24±1.41)%,他莫昔芬的包封率为(93.14±2.67)%。结论:优化所得处方为多西他赛他莫昔芬复方脂质体的开发提供了基础保证。

Objective:To optimize the formulation of docetaxel-tamoxifen liposomes.Methods:Single factor test was used to investigate the liposome-drug ratio,soybean phospholipid/cholesterol ratio and tamoxifen citrate/docetaxel ratio on the liposomal particle size,Zeta potential,dispersion index(PdI),drug encapsulation efficiency and drug loading.A two-factor five-level star-point designresponse surface method was used to optimize the formulation with drug encapsulation efficiency and drug loading as the indices.Results:The optimal formulation was lipids/drug(19∶1)and SPC/chol(9∶1).The average entrapment efficiency of DTX and TMX in liposomes was(82.24±1.41)%and(93.14±2.67)%,respectively.Conclusion:The optimal formulation provides a basis for the development of new administration routes and dosage forms of docetaxel-tamoxifen liposomes.