多烯紫杉醇长循环脂质体的制备工艺优选及体外释放性能考察  

Optimization of Preparation Technology for Long-circulating Liposomes of Docetaxeland Investigation of Its in vitro Release Properties

作　　者：陈宇潮 程怡[1] 仝一丹 陈静[1] 

机构地区：[1]广州中医药大学中药学院,广州510006

出　　处：《中国实验方剂学杂志》2014年第12期6-9,共4页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(30772790)

摘　　要：目的:优选多烯紫杉醇长循环脂质体(DPL)的处方与制备工艺并考察其体外释药性能。方法:以蛋黄卵磷脂(EPC)、胆固醇(CH)和聚乙二醇2000-二硬脂酰磷脂酰乙醇胺(PEG 2000-DSPE)为膜材,采用薄膜分散-高压均质法制备DPL。通过单因素试验确定均质压力和均质循环次数,正交试验筛选处方工艺;利用透析法测定脂质体包封率,透射电镜观察脂质体形态,动态光散射粒度分析仪测定脂质体粒径分布与Zeta电位,考察DPL的体外释放规律。结果:最佳处方为药物-类脂(1∶5),EPC-CH(4∶1),PEG 2000-DSPE加入量4%;高压均质条件为50 MPa,循环数3次;DPL包封率(97.44±1.33)%,平均粒径(162.17±2.63)nm,平均Zeta电位(-14.54±1.82)mV;DPL在48 h内仅释放65%,体外药物释放符合Weibull方程。结论:采用PEG 2000-DSPE作为长循环材料可增大脂质体的粒径,DPL具有一定缓释作用。Objective： To optimize preparation and formulation technology of long-circulating liposomes of docetaxel （DPL） and investigate its in vitro release properties. Method： Using egg phosphatidylcholine （EPC） , cholesterol （CH） and polyethylene glycol 2000-distearoyl phosphatidylethanolamine （PEG 2000-DSPE） as raw materials, DPL was prepared by film dispersion-high pressure homogenization technique. Homogenization pressure and recurring number were determined by single factor tests, orthogonal design was used to select formulation. Encapsulation efficiency of liposomes was determined by dialysis, transmission electron microscopy was used to observe morphous and dynamic light scattering particle size meter was used to detect particle distribution and Zeta potential, then in vitro release conducts of liposomes were investigated. Result： Optimal preparation and formulation conditions were as follows ： drug-lipid （ 1 ： 5 ）, EPC-CH （ 4 ： 1 ） , PEG 2000-DSPE added in an amount of 4%. Homogenization pressure of 50 MPa for 3 times; under these conditions, average encapsulation efficiency of DPL was （97.44 ± 1.33）% , average particle size was （ 162. 17±2.63） nm and Zeta potential was （ -14.54 ± 1.82） mV; DPL released 65% in 48 h, in vitro release curve of DPL was fitted with Weibull equation. Conclusion： PEG 2000-DSPE could increase particle size of liposimes as long-circulating material,DPL had a sustained release effect.

关 键 词：多烯紫杉醇 长循环脂质体 包封率 体外释放性能 薄膜分散-高压均质法 

分 类 号：R283.6[医药卫生—中药学]