紫杉醇的pH敏感聚合物胶束的制备及其体外释放研究  

Preparation and in vitro release evaluation of paclitaxel-loaded pH-sensitive polymeric micelle

作　　者：王子琪[1] 王狄狮 李馨儒[1] 屈小又 何楚瑜 邹洋 邓运强 周艳霞[1] 刘艳[1] 

机构地区：[1]北京大学药学院分子药剂学与新释药系统北京市重点实验室,北京100191

出　　处：《中国新药杂志》2018年第4期459-464,共6页Chinese Journal of New Drugs

摘　　要：目的:合成聚(2-乙基-2-噁唑啉)-聚乳酸(PEOz-PLA)嵌段共聚物,制备包载紫杉醇的PEOzPLA聚合物胶束,并对其理化性质进行评价。方法:采用开环聚合法合成PEOz-PLA,利用核磁共振确证共聚物的结构,并用芘荧光探针法测定该共聚物的临界胶束浓度,GPC测定其相对分子质量。采用薄膜水化法制备载紫杉醇的PEOz-PLA胶束,通过动态光散射法测定胶束的粒径,用透射电镜观察胶束的形态,采用透析法对胶束的体外释放行为进行考察。结果:紫杉醇聚合物胶束的平均粒径为(41.83±3.55)nm,粒径分布较窄。电镜观察结果表明,紫杉醇聚合物胶束呈球形,粒径大小较均匀。胶束的包封率和载药量分别为(99.5±0.2)%和(5.0±0.1)%。体外释放的结果表明,紫杉醇自胶束中释放的速率随着释放介质p H的降低而逐渐加快。结论:载紫杉醇的PEOz-PLA聚合物胶束具有优良的理化性质和明显的p H依赖性释放特征,可作为抗肿瘤药物的递送载体。Objective： To synthesize poly（ 2-ethyl-2-oxazoline）-poly（ D,L-lactide）（ PEOz-PLA） diblock copolymer,prepare paclitaxel-loaded PEOz-PLA polymeric micelles and evaluate their physicochemical properties.Methods： PEOz-PLA was synthesized through a two-step reaction by ring-opening polymerization and characterized.Nuclear magnetic resonance was used to reveal the construction of PEOz-PLA,then the critical micelle concentration was evaluated by pyrene fluorescence probe method. The molecular weight of PEOz-PLA polymer was determinate by gel permeation chromatography. Paclitaxel-loaded PEOz-PLA micelles were prepared by film-hydration method.The particle size and size distribution were determined by dynamic light scattering. The morphology of the micelles was observed through transmission electron microscope（ TEM）. The in vitro release of paclitaxel（ PTX） from PEOz-PLA micelles was evaluated using dialysis method. Results： The mean size of PTX-loaded PEOz-PLA micelles was（ 41. 83 ± 3. 55） nm in diameter with a narrow distribution. TEM images showed that PEOz-PLA micelles exhibited a well-defined spherical shape with uniform size. The encapsulation efficiency and drug loading content for the micelles were（ 99. 5 ± 0. 2） % and（ 5. 0 ± 0. 1） %,respectively. The release of paclitaxel from the micelles was found to be p H-dependent and increased with decrease of p H value. Conclusion： PEOz-PLA micelles exhibit remarkably p H-dependent release behavior and may be a potential carrier for tumor targeted delivery of antitumor drugs.

关 键 词：紫杉醇 PH敏感性 聚合物胶束 体外释放 

分 类 号：R979.1[医药卫生—药品]