有机化学 ›› 2013, Vol. 33 ›› Issue (12): 2520-2527.DOI: 10.6023/cjoc201310043 上一篇    下一篇

研究论文

PPEGMEA-g-PBLG两亲性接枝共聚物的合成及其作为阿霉素输送载体的研究

蔡晓冰a, 胡薇b, 陆国林c, 黄晓宇c   

  1. a 同济大学附属上海第十人民医院骨科 上海 200072;
    b 第二军医大学附属长海医院普四科 上海 200433;
    c 中国科学院上海有机化学研究所 上海 200032
  • 收稿日期:2013-10-26 修回日期:2013-11-11 出版日期:2013-12-25 发布日期:2013-11-14
  • 通讯作者: 胡薇, 黄晓宇 E-mail:huweicj@163.com;xyhuang@mail.sioc.ac.cn
  • 基金资助:

    国家自然科学基金(Nos. 81171737,21174158)资助项目.

Synthesis of PPEGMEA-g-PBLG Amphiphilic Graft Copolymer and Its Research as Doxorubicin Delivery Vectors

Cai Xiaobinga, Hu Weib, Lu Guolinc, Huang Xiaoyuc   

  1. a Department of Orthopedics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072;
    b Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433;
    c Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032
  • Received:2013-10-26 Revised:2013-11-11 Online:2013-12-25 Published:2013-11-14
  • Supported by:

    Project supported by the National Natural Science Foundation of China (Nos. 81171737, 21174158).

首先利用单电子转移活性自由基聚合(SET-LRP)制备了聚甲基醚聚乙二醇丙烯酸酯(PPEGMEA)主链,再通过二异丙基氨基锂(LDA)攫取羰基α-位活泼氢合成了含溴的PPEGMEA-Br,通过亲核取代反应和还原反应两步制备得到了大分子开环聚合引发剂PPEGMEA-NH2. 然后采用grafting-from策略,PPEGMEA-NH2引发γ-苄基-L-谷氨酸酯五元环酸酐(BLG-NCA)的开环聚合,合成了结构规整的两亲性接枝共聚物PPEGMEA-g-PBLG. 接着,以PPEGMEA-g-PBLG为药物载体,负载了阿霉素(DOX). 利用紫外吸收光谱法测定了载药胶束的载药量,载药胶束的载药量最高可达到32.3%,载药胶束的体外药物释放具有很好的药物缓释特性.

关键词: 两亲性接枝共聚物, 单电子转移活性自由基聚合, 阿霉素:药物载体

The poly[poly(ethylene glycol) methyl ether acrylate] (PPEGMEA) backbone was first prepared by single electron transfer-living radical polymerization (SET-LRP). The backbone was treated with lithium diisopropylamide (LDA) and 2-bromoisobutyryl bromide at -78 ℃ to give Br-containing PPEGMEA-Br. PPEGMEA-NH2 macroinitiator was then prepared by successive substitution and reduction reactions. A series of well-defined PPEGMEA-g-PBLG graft copolymers were synthesized by ring-opening graft polymerization of γ-benzyl-L-glutamate-N-carboxyanhydride (BLG-NCA) via grafting-from technique. A series of doxorubicin (DOX)-loaded polymeric micelles based on PPEGMEA-g-PBLG amphiphilic graft copolymers were prepared. The drug loading content (DLC) was measured by UV and the DLC of polymeric micelles was found to be as high as 32.3%. The drug release in vitro showed good delayed drug release feature.

Key words: amphiphilic graft copolymer, single electron transfer-living radical polymerization, doxorubicin, drug carrier