Novel PLGGE graft polymeric micelles for doxorubicin delivery  

作　　者：YU ZuXiao HE Bin SHENG MingMing WANG Gang GU ZhongWei 

机构地区：[1]National Engineering Research Center for Biomaterials,Sichuan University,Chengdu 610064,China [2]College of Material and Chemical Engineering,Sichuan University of Science&Engineering,Zigong 643000,China

出　　处：《Chinese Science Bulletin》2012年第31期3994-4004,共11页

基　　金：supported by the National Basic Research Program of China (2011CB606206);the National Natural Science Foundation of China(50830105, 51133004 and 31170921);the Key Program for the International S&T Collaboration Projects of China (2010DFA51550);the Program for New Century Excellent Talents in University, Ministry of Education (NCET-10-0564);Department of Education of the Sichuan Province, China (09ZC056)

摘　　要：Novel poly{(lactic acid)-co-[(glycolic acid)-alt-(L-glutamic acid)]}-g-monomethyl poly(ethylene glycol) (PLGGE) micelles were prepared and used as carriers for anti-tumor drug delivery. Three PEGylated PLGG copolymers (PLGGE2000, PLGGE1100 and PLGGE500) were characterized by XRD, TG and DSC. The critical micelle concentrations (CMCs) of the amphiphilic copolymers were 1.04, 0.55 and 0.13 μg/mL, respectively. The TEM, AFM and DLS measurements revealed that the micelles were homogeneous spherical nanoparticles with the diameters ranged from 50 to 150 nm when THF was used as solvent in the preparation of the micelles. Interestingly, extended cylindrical micelles were obtained using CHCl 3 as solvent. The micelles could trap doxorubicin (DOX) in the core with the highest drug loading content up to 23.7%. The mean diameter of drug loaded micelles was much bigger than that of blank micelles. The in vitro drug release of the micelles was diffusion-controlled release within the first 36 h and initial burst release was not obvious. However, after 36 h, the release rate in pH 5.0 was faster than that in pH 7.4 due to the degradation. The PLGGE micelles were nontoxic to both NIH 3T3 fibroblasts and HepG2 cells. The in vitro cytotoxicity against HepG2 cells demonstrated that the drug loaded micelles exhibited high inhibition activity to cancer cells. CLSM observation of HepG2 cells showed that DOX released from the micelles could be delivered into cell cytoplasm and cell nuclei. PLGGE micelles are potential promising carriers for anti-tumor drug delivery.Novel poly{（lactic acid）-co-[（glycolic acid）-alt-（L-glutamic acid）] }-g-monomethyl poly（ethylene glycol） （PLGGE） micelles were prepared and used as carriers for anti-tumor drug delivery. Three PEGylated PLGG copolymers （PLGGE2000, PLGGE1100 and PLGGE500） were characterized by XRD, TG and DSC. The critical micelle concentrations （CMCs） of the amphiphilic copoly- mers were 1.04, 0.55 and 0.13 gg/mL, respectively. The TEM, AFM and DLS measurements revealed that the micelles were ho- mogeneous spherical nanoparticles with the diameters ranged from 50 to 150 nm when THF was used as solvent in the prepara- tion of the micelles. Interestingly, extended cylindrical micelles were obtained using CHC13 as solvent. The micelles could trap doxorubicin （DOX） in the core with the highest drug loading content up to 23.7%. The mean diameter of drug loaded micelles was much bigger than that of blank micelles. The in vitro drug release of the micelles was diffusion-controlled release within the first 36 h and initial burst release was not obvious. However, after 36 h, the release rate in pH 5.0 was faster than that in pH 7.4 due to the degradation. The PLGGE micelles were nontoxic to both NIH 3T3 fibroblasts and HepG2 cells. The in vitro cytotoxi- city against HepG2 cells demonstrated that the drug loaded micelles exhibited high inhibition activity to cancer cells. CLSM ob- servation of HepG2 cells showed that DOX released from the micelles could be delivered into cell cytoplasm and cell nuclei. PLGGE micelles are potential promising carriers for anti-tumor drug delivery.

关 键 词：聚合物胶束 阿霉素 HepG2细胞 交付 两亲性共聚物 激光共聚焦显微镜 透射电子显微镜 聚乙二醇化 

分 类 号：R943[医药卫生—药剂学]