两亲性六臂星型端氨基PEG-PLGA的合成、表征及胶束化行为

采用本体开环聚合法,以乙交酯(GA)和DL-丙交酯(DLA)为原料,肌醇为引发剂,合成了一系列不同分子量的六臂星型聚乳酸聚乙醇酸(PLGA)(6-s-PLGA50,6-s-PLGA100,6-s-PLGA200,其中50,100,200为原料与引发剂的摩尔比),采用羧基化反应对其端基进行羧化处理.以聚乙二醇4000(PEG4000)为原料用对甲苯磺酰化法得到sTO-PEG-OTs,再进行氨解得到双端氨基PEG(H2N-PEG-NH2).末端羧基6-s-PLGAx通过N-环己基碳二亚胺(DCC)缩合反应与双端氨基PEG连接得到两亲性星型六臂结构的聚合物(6-s-PLGAx-PEG-NH2).分别用核磁共振氢谱法(1H NMR)、凝胶排阻色谱法(GPC)及差示热量热分析法(DSC)等手段对6-s-PLGAx和6-s-PLGAx-PEG-NH2进行了表征.以6-s-PLGA100-PEG-NH2聚合物为例,自组装得到空白的纳米粒子,并用透射电子显微镜法(TEM)和动态光散射法(DLS)考察了粒子的表面形态以及粒径分布特征,用1H NMR分析了胶束的"核-壳"结构.用噻唑蓝四氮唑溴化物(MTT)比色法探讨了该两亲性材料的体外细胞毒性.研究结果表明,合成了不同分子量的两亲性六臂星型端氨基PEG-PLGA,该两亲性聚合物可自组装形成纳米胶束,粒径范围在40～60 nm,与PLGA相比体外细胞毒性无显著性差异.

Synthesis, Characterization and Micellization of Star-shaped Amphiphilic Block Copolymer 6-s-PLGAx-PEG-NH2

The star-shaped poly(lactide-co-glycolide)(PLGA) was synthesized via the ring-opening polymerization of D,L-lactide and glycolide, with inositol as a multifunctional initiator and stannous 2-ethylhexanoate as a catalyst. Amine-terminated poly(ethylene glycol)(NH2-PEG-NH2) was synthesized using improved Gabriel method, in which the end hydroxyl groups were converted to amino groups. A series of 6-s-PLGAx-PEG-NH2 was prepared using classical DCC condensation reaction in the mild condition. The structures of these polymers were characterized by 1H NMR spectroscopy, while the molecular weight and polydispersity index(PDI) were determined by gel permeation chromatography(GPC). The glass transition temperature(Tg) of copolymer was determined by differential scanning calorimetry(DSC). The NH2-PEG-NH2 was characterized using IR and element analyses, the result of element analysis proved that the hydroxyl conversion was up to 90%. Nanoparticles(NPs) were prepared by solvent evaporation method, 1H NMR was used to analysis the structure of the NPs, dynamic light scatering(DLS) for the size and size distribution, transition electron microscope(TEM) for the morphology of the NPs. The biocompatibility was detected with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltertrazolium bromide(MTT) assay. The results showed success of synthesis of star-shaped amphiphilic block copolymer 6-PLGAx-PEG-NH2. The new polymer has good biocompatibility and can formulate micelles easily. It may be used as a new drug carrier for drug controlled system.