两亲性六臂星型端氨基PEG-PLGA的合成、表征及胶束化行为

Synthesis,Characterization and Micellization of Star-shaped Amphiphilic Block Copolymer 6-s-PLGA_x-PEG-NH_2

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.

The star-shaped poly （lactide-co-glycolide） （PLGA） was synthesized via the ring-opening poiymeri-zation of D,L-lactide and glycolide, with inositol as a muhifunctional 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 in- dex （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 mi-croscope（TEM） for the morphology of the NPs. The biocompatibility was detected with 3-（4,5-dimethyhhia- zol-2-yl）-2,5-diphenyltertrazolium bromide （MTF） 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.