新型药物载体材料——端羟基聚(丙交酯-co-对二氧环己酮)的合成与表征

Synthesis and characterization of a novel drug carrier material——hydroxyl-terminated poly(lactide-co-p-dioxanone)

聚乳酸(PLA)作为药物载体材料存在因疏水性强而导致的药物释放速率难控以及在循环系统中停留时间短等问题。研究表明,在PLA中引入乙醇酸(GA)可提高材料降解速率,引入聚乙二醇(PEG)则可延长共聚物在循环系统中的停留时间。研究以丙交酯(LA)和对二氧环己酮(PDO)为主要原料,在辛酸亚锡-乙二醇共引发体系的存在下,通过熔融开环聚合制备出了端羟基聚(丙交酯-co-对二氧环己酮)(HO-P(LA-co-PDO)-OH)。这种同时具有PLA、GA和EG结构单元的大分子二醇可望成为一种降解速率可控、在循环系统中停留时间可调的新型药物载体材料。采用DSC、1HNMR、13CNMR和GPC-MALLs等对其结构和热学性能进行了表征。分子量检测结果表明,HO-P(LA-co-PDO)-OH的分子量随原料中PDO/LA摩尔比的减小而增大。

The incorporation of glycolic acid （GA） into polylactic acid （PLA） resulted in fastened and controllable degradation rate of the obtained copolymer, and the copolymerization of poly（ethylene glycol） （PEG） with PLA produced block copolymers exhibiting extended residence time in circulation systems. In this study, p- dioxanone （PDO） was employed to copolymerize with DL-lactide （LA） via ring-opening melt polymerization using Sn（Oct）2 as an initiator and ethylene glycol as a co-initiator. The obtained hydroxyl-terminated poly（laetide-co-p-dioxanone） copolymers （HO-P（LA-co-PDO）-OH） were such a eopolymer consisting of PLA, GA and EG, hopefully becoming a novel drug carrier material integrating controllable degradation rate together with extended residence time. 1H NMR, 13C NMR, DSC and GPC-MALLS were employed to characterize the copolymers, and the effect of PDO/LA molar ratios in the feedstock was investigated on the molecular weights of HO- P（LA-co-PDO）-OH. The results confirmed the successful synthesis of HO-P（LA-co-PDO）-OH and revealed that the molecular weights of HO-P（LA-co-PDO）-OH increased with decreasing PDO/LA ratios.