四臂聚乙二醇-聚丙交酯立体复合胶束及其药物传输性能  

Stereocomplex Micelles Based on 4-Armed Poly( ethylene glycol)-Polylactide Enantiomeric Copolymers for Drug Delivery

作　　者：刘东红[1,2] 丁建勋[2] 许维国[2] 宋晓峰[1] 庄秀丽[2] 陈学思[2] 

机构地区：[1]长春工业大学化学工程学院,长春130012 [2]中国科学院长春应用化学研究所中国科学院生态环境高分子材料重点实验室,长春130022

出　　处：《高分子学报》2014年第9期1265-1273,共9页Acta Polymerica Sinica

基　　金：国家自然科学基金(基金号51303174、51321062和51233004);吉林省科技发展计划(项目号20130102065JC);吉林省教育厅十二五规划项目(项目号20140123)资助项目

摘　　要：以异辛酸亚锡为催化剂,通过四臂聚乙二醇(4-armed PEG)引发右旋丙交酯(DLA)或左旋丙交酯(LLA)开环聚合合成四臂PEG-PLA对映体共聚物.通过纳米沉淀的方法制备了四臂PEG-b-PDLA胶束(PDM)、四臂PEG-b-PLLA胶束(PLM)和四臂PEG-b-PDLA/四臂PEG-b-PLLA立体复合胶束(SCM),并对其形貌、粒径、稳定性和立体复合机理等进行系统表征.以阿霉素(DOX)为模型抗肿瘤药物载入胶束中,与PDM和PLM相比,SCM具有更优异的药物负载能力.与DOX相比,载药四臂PEG-PLA胶束,尤其是负载DOX的SCM,表现出更优异的肿瘤细胞增殖抑制效果,作用更持久,并且对正常细胞的毒性较小,从而揭示了其作为潜在抗肿瘤药物载体的良好前景.In this study,the stereocomplex micelles derived from nonlinear poly（ethylene glycol）-polylactide （PEG-PLA） enantiomeric copolymers were designed and prepared for drug delivery. First,the 4-armed PEG- PLA enantiomeric copolymers were synthesized through the ring-opening polymerization of D-lactide （DLA） and L-lactide （LLA） with 4-armed PEG as maeroinitiator and stannous octoate as catalyst. 4-Armed PEG-b- PDLA micelle （ PDM ）, 4-armed PEG-b-PLLA micelle （ PLM ） and 4-armed PEG-b-PDLA/4-armed PEG-b- PLLA stereocomplex micelle （SCM） were prepared through nanoprecipitation, and the morphologies,sizes and stereocomplex mechanisms of micelles were systemically characterized. It was found that the SCM showed more compact structure,smallert dynamic diameter and critical micellization concentration in contrast to PDM and PLM. Doxorubicin （DOX） , a model antitumor drug, was loaded into mieelles, and SCM exhibited the best drug loading capability compared with PDM and PLM. In addition, the DOX-loaded 4-armed PEG-PLA micelles, especially SCM, showed more efficient and durable capabilities for malignant cellular proliferation inhibition （e. g., HepG2 cells, a human hepatoma cell line） , and exhibited less toxicities toward normal cells（ e. g., L929 cells,a mouse fibroblast cell line） , which revealed the great prospect of SCM for potential antitumor drug delivery.

关 键 词：恶性肿瘤治疗 控制释放 立体复合胶束 聚丙交酯 纳米沉淀 

分 类 号：O631.3[理学—高分子化学] TQ460.1[理学—化学]