注射用紫杉醇聚合物胶束稳定性的研究  

Physical stability of paclitaxel-loaded polymeric micelles for injection*

作　　者：林琳[1] 涂家生[1] 庞卉[1] 苗先烽[1] 何威[1] 

机构地区：[1]中国药科大学药剂教研室,南京210009

出　　处：《药学与临床研究》2009年第2期85-89,共5页Pharmaceutical and Clinical Research

基　　金：江苏省高新技术发展计划资助项目(编号:59637050);国家科技支撑计划(编号:2008BA155B03)

摘　　要：目的:从聚合物胶束动力学稳定性机制出发,研究制备温度及贮存温度对以PLA-mPEG为载体的紫杉醇聚合物胶束物理稳定性的影响。方法:通过DSC法考察PLA-mPEG疏水嵌段的玻璃化温度,通过荧光偏振法、荧光光谱法及1H-NMR谱图分别考察PLA-mPEG疏水嵌段粘度、极性及其链段移动性随温度的变化;采用熔融蒸发法制备紫杉醇聚合物胶束,建立了以T1和K为参数的紫杉醇胶束稳定性考察方法,并考察其在不同制备及贮存温度下物理稳定性的变化。结果:在玻璃化温度附近,PLA-mPEG聚合物胶束疏水嵌段的粘度较小,核嵌段迁移较剧烈,极性较大;而通过熔融蒸发法制备的紫杉醇载药聚合物胶束在玻璃化温度附近,即50℃下水化后物理稳定性较好,贮存温度在4℃物理稳定性较好,符合基于紫杉醇载药聚合物胶束微观性质的结果对其物理稳定性的预测。结论:聚合物胶束动力学稳定性的机理,对制备稳定的紫杉醇载药胶束有着重要的指导意义。Objective： To prepare poly （ D, L-lactic acid）-poly （ethylene glycol） methyl ether （ PLA- mPEG） polymeric micelles and to study the factors affecting the physical stability of paclitaxel （PTX）- loaded polymeric micelles based on the mechanism of kinetic stability. Methods ： The micro-characteristics such as glass-transition temperature, the viscosity, segmental motion, polarity of the hydrophobic bloek of PLA-mPEG were identified separately by DSC, fluorescence polarization, ^1 H-NMR and spectrofluorometry. The PTX-loaded polymeric micelles were prepared by solvent evaporation-solid melting method. HPLC was used to determine the stability of PTX in the polymeric micelles, with T, and K as parameters. Moreover, physical stability of PTX loaded PLA-mPEG was studied in different hydration temperatures and storage temperatures. Results： Close to the glass-transition temperature, hydrophobic PLA block had the least viscosity, the strongest polarity and the most intense segmental motion. PTX-loaded PLA-mPEG polymeric micelles had better physieal stability with hydration temperature at 50 ℃ （above its glass-transition temperature） and with storage temperature at 4℃, as expected by the micro-characteristics. Conclusion： Kinetic stability mechanism of polymeric micelles is the good guide for the preparation of stable PTX-loaded polymeric micelles.

关 键 词：物理稳定性 玻璃化温度 聚合物胶束 聚乙二醇单甲醚-聚乳酸 疏水嵌段 紫杉醇 

分 类 号：R944.7[医药卫生—药剂学] R927.11[医药卫生—药学]