可注射PLLA-mPEG水凝胶的制备及性能研究

摘要

The star-shaped poly-L-lactide (PLLA) was synthesized via ring-opening polymerization of L-lactide using pentaerythritol as the initiator. A series of star-shaped PLLA-mPEG copolymers were synthesized from the carboxylated star-shaped PLLA and mPEG by the"core first"method. Their composition, structure, and molecular weight were characterized via 1HNMR and GPC techniques. The sol-gel transition temperatures were determined with the test tube inverting method, which was from 20 to 66°C. Phase-change characteristics of the copolymers strongly depended on the molecular weight of mPEG. The sol-gel transition temperatures increased with larger molecular weight of mPEG. When the molecular weight of mPEG was 350, the copolymer have desirable sol-gel transition temperatures between 20 and 45℃. DLS and dye probe techniques were employed to identify the formation of micelles of copolymers in aqueous solutions, which was driven by hydrophobic force. The in vitro study of drug release indicated that the Urapidil Hydrochloride-PLLA-mPEG hydrogels exhibited significant sustained-release capability, and its release kinetics could be described by the first order equation.%采用先核后臂方法，以季戊四醇引发丙交酯开环聚合制备了星型聚乳酸(PLLA)，将末端羧基化的星型 PLLA与聚乙二醇单甲醚(mPEG)反应，合成了一系列星型PLLA-mPEG共聚物。通过1H-NMR和GPC对其组成、结构及分子量进行了表征。采用试管翻转法得到了 PLLA-mPEG 共聚物水溶液的相转变温度，相变范围在20~66℃。水凝胶相变温度与mPEG分子量有很大关系，当mPEG分子量为350时，共聚物的相变范围为20~45℃。随着mPEG分子量增大水凝胶相变温度逐渐提高。利用激光粒度分析和染料探针方法证实了共聚物先自组装形成胶束，然后聚集使sol-gel发生相转变，疏水作用力是相变内在的驱动力。体外药物释放结果表明，星型PLLA-mPEG水凝胶对所包载的盐酸乌拉地尔具有明显的缓释作用，释药动力学满足一级动力学模型。