聚乳酸-聚乙二醇三嵌段共聚物包载紫杉醇纳米胶束的制备及其体外药物释放行为  

Preparation and Drug Release Behavior of Paclitaxel Loaded Polylactide-poly(ethylene glycol)Triblock Copolymer Micelles

作　　者：齐旭[1] 刘佩[1] 李速明[1] 范仲勇[1] 

机构地区：[1]复旦大学材料科学系,上海200433

出　　处：《复旦学报（自然科学版）》2013年第1期1-8,共8页Journal of Fudan University：Natural Science

基　　金：国家重点基础研究发展计划(973计划)资助项目;国家自然科学基金资助项目(51073041)

摘　　要：以聚乙二醇和丙交酯为原料,合成了一系列分子量的聚乳酸聚乙二醇三嵌段共聚物.分别采用直接溶解法和溶剂挥发/薄膜水化法制备了包载抗癌药物紫杉醇的纳米胶束.用DLS和SEM观测纳米胶束的形态,采用HPLC研究载药胶束的载药量、包封率,在体外磷酸缓冲盐(pH 7.4),37℃模拟条件下研究载药胶束的体外释放行为,MTT法研究了空白胶束的细胞毒性以及载药胶束对C6细胞的体外抑制.结果表明使用直接溶解法得到粒径为200nm的球形胶束,使用溶剂挥发/薄膜水化法得到粒径分别为50nm和150nm的纳米胶束;溶剂挥发/薄膜水化法的载药量和包封率高于直接溶解法,缓释曲线均符合Ritger-Peppas指数模型;材料和制备方法均未引入细胞毒性,采用直接溶解法制备的载药胶束与游离紫杉醇对脑胶质瘤细胞C6的抑制效果相当.PLA PEG triblock copolymers with different molecular weights were synthesized from lactide and dihydroxyl PEG. Paclitaxel（PTX）loaded eopolymer micelles were prepared by the direct dissolution or the solvent evaporation followed by membrane hydration methods. The sizes and structures of micelles were determined by dynamic light scattering （DLS） and scanning electron microscope （SEM）. Drug encapsulation efficiency （EE） and loading content（LC）of micelles were evaluated by high-performance liquid chromatography（HPLC）. In vitro release was performed in phosphate buffered saline（pH 7.4）at 37℃ The cytotoxicity of blank micelles and drug loaded micelles was evaluated by MTT method. The size of micelles by direct dissolution was approximately 200 nm, while solvent evaporation yielded two micelle populations about 50 nm and 150 nm diameters. Higher EE and LC values were obtained for micelles by solvent evaporation compared with those by direct dissolution. Release curves of drug loaded micelles were well fitted by Ritger-Peppas exponential model. No harm was introduced by copolymers and the preparation methods. MTT results showed that the copolymers and the preparation methods present no cytotoxicity. Similar C6 glioma dose-effect curves were obtained for PTX loaded micelles by direct dissolution and free PTX.

关 键 词：聚乳酸 聚乙二醇 胶束 紫杉醇 缓释 

分 类 号：O633.1[理学—高分子化学]