双亲支链梳形共聚物的合成及其自乳化负载药物性能  

Synthesis of Amphiphilic Centipede-Like Copolymer as Self-Emulsifying Nano-Drug Carriers

作　　者：朱绍林 邵建铭 何卫东[1] 

机构地区：[1]中国科学技术大学高分子科学与工程系,合肥230026

出　　处：《功能高分子学报》2017年第3期265-273,共9页Journal of Functional Polymers

摘　　要：通过可逆加成-断裂链转移(RAFT)聚合制备出聚甲基丙烯酸缩水甘油酯(PGMA),经过叠氮钠与PGMA环氧基团的反应引入叠氮基和羟基,然后依次通过端炔基聚乙二醇(PEG-alk)与叠氮基的点击反应,己内酯(CL)在羟基存在下的开环聚合反应,获得双亲支链梳形共聚物(PGMA-g-PEG/PCL)。利用该梳形共聚物的两亲性,在氯仿-水混合体系中,进行自乳化高效负载阿霉素(DOX),得到负载DOX的纳米粒子。利用核磁共振氢谱、红外光谱和凝胶渗透色谱确认了最终产物及其前体聚合物的结构。利用动态光散射、紫外可见分光光度计和扫描电镜研究该载药粒子在pH为7.0和5.0的水溶液中的释放。结果表明:该纳米粒子平均粒径约为100nm,该粒子能有效释放DOX,在酸性条件下释放速率加快,且伴随PCL的降解。Amphiphilic centipede-like copolymer and doxorubicin-loading nanoparticle were prepared through self-emulsification.Then,narrowly distributed poly （glycidyl methacrylate）（PGMA） was prepared through reversible addition-fragmentation-transfer （RAFT） polymerization and converted into PGMA with hydroxyl and azido group at each GMA unit （PGMA-OH/N_3）.Thereafter,poly （ethylene glycol） capped with one alkynyl group（PEG-alk）was grafted onto PGMA backbone through click reaction to result in PGMA-OH/PEG,and poly （ε-caprolactone）（PCL） was grafted from PGMA via SnOct2-initiated ring-opening polymerization of CL monomer.Thus,amphiphilic centipede-like copolymer of PGMA-g-PEG/PCL was successfully obtained,confirmed with proton Nuclear Magnetic Resonance （~1 HNMR） spectroscopy,Fourier Transfer Infra-red （FT-IR） spectroscopy and Gel Permeation Chromatography （GPC）.Based on the amphiphilicity of PGMA-g-PEG/PCL,its self-emulsification in water-chloroform mixture could load doxorubicin（DOX） efficiently to form nanoparticles with averaged radius of about 100 nm,which was determined by Dynamic Light Scattering（DLS） and scanning electron microscopy after the evaporation of chloroform.With the aid of UV-Vis spectroscopy and DLS,the drugreleased of those nanoparticles was performed in neutral and acidic aqueous solutions（pH=7.0and 5.0）.Results showed that higher release rate was achieved under acidic condition due to the degradation of PCL.

关 键 词：双亲性梳形共聚物 纳米药物载体 自乳化 点击反应 RAFT聚合 

分 类 号：O63[理学—高分子化学]