PNIPAM-b-聚碳酸酯温敏胶束的制备及用作药物控制释放载体的研究

SYNTHESIS AND CHARACTERIZATION OF PNIPAM-b-POLYCARBONATE COPOLYMERS AS SELF-ASSEMBLED THERMOSENSITIVE MICELLES FOR DRUG DELIVERY

以多孔硅球固定化猪胰脂肪酶(IPPL)为催化剂,温敏性HO-PNIPAM为大分子引发剂,5-甲基-5-烯丙氧羰基-三亚甲基碳酸酯(MAC)和5,5-二甲基三亚甲基碳酸酯(DTC)为共聚单体,通过开环聚合合成了不同结构比例的两亲性嵌段型共聚物P(MAC-co-DTC)-b-PNIPAM.该嵌段型共聚物在水中可自组装形成稳定的胶束,其CMC值为20～60 mg/L,干态粒径20～70 nm,LCST值为38～43℃,细胞毒性实验显示其具有良好的生物相容性.以疏水性药物醋酸泼尼松为模型药物,研究了嵌段型共聚物胶束对药物的负载及释放行为,结果表明载药胶束具有良好的温敏性药物释放性能.

A series of poly（N-isopropylacrylamide）（PNIPAM）-blocked polycarbonates,P（MAC-co-DTC）-b-PNIPAM,were designed as thermosensitive micelles for drug delivery.The amphiphilic block copolymers were synthesized by enzymatic ring-opening copolymerization of HO-PNIPAM,5-methyl-5-allyloxycarbonyl-trimethylene carbonate（MAC） and 5,5-dimethyltrimethylene carbonate（DTC）.The novel block copolymers were characterized by1H-NMR and GPC-MALLS analyses.All the amphiphilic copolymers were able to self-assemble into nano-sized micelles in aqueous solutions with hydrophilic PNIPAM shells and hydrophobic polycarbonates cores.The critical micelle concentration（CMC） determined by fluorescence spectroscopy using pyrene as a probe was around 20~60 mg/L.Transmission electron microscopy（TEM） measurements showed that the micelles presented even spherical shape and the diameters of them were about 20~70 nm.The micelles exhibited thermosensitivity at lower critical solution temperature（LCST） of around 38~43℃,which was related to the hydrophilic PNIPAM blocks.In vitro experiments demonstrated that the P（MAC-co-DTC）-b-PNIPAM showed low cytotoxicity.Furthermore,the micelles were loaded with hydrophobic drug of prednisone acetate（PA） and in vitro drug release investigation also displayed thermosensitivity.The results suggested that P（MAC-co-DTC）-b-PNIPAM copolymers would be a promising thermosensitive carrier for drug delivery.