有机化学 ›› 2015, Vol. 35 ›› Issue (12): 2529-2536.DOI: 10.6023/cjoc201509032 上一篇    下一篇

研究论文

医用生物相容性接枝共聚物负载阿霉素和香豆素的研究

钱文昊a,b, 苏俭生a, 龚雪a, 叶茂b, 徐培成b   

  1. a 上海牙组织修复与再生工程技术研究中心 同济大学口腔医学院口腔修复学教研室 上海 200072;
    b 上海市徐汇区牙病防治所 上海 200032
  • 收稿日期:2015-09-25 修回日期:2015-10-09 发布日期:2015-10-13
  • 通讯作者: 苏俭生, 徐培成 E-mail:sjs@tongji.edu.cn;xpc1238@126.com
  • 基金资助:

    国家自然科学基金(Nos. 81371949, 81572114)和上海市生物医药科技重点(No. 13411951200)资助项目.

Studies on Loading Doxorubicin and Coumarin by Medical Biocompatible Graft Copolymer

Qian Wenhaoa,b, Su Jianshenga, Gong Xuea, Ye Maob, Xu Peichengb   

  1. a Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Department of Prosthodontics, School of Stomatology, Tongji University, Shanghai 200072;
    b Department of Stomatology, Shanghai Xuhui District Dental Center, Shanghai 200032
  • Received:2015-09-25 Revised:2015-10-09 Published:2015-10-13
  • Supported by:

    Project supported by the National Natural Science Foundation of China (Nos. 81371949 and 81572114) and the Shanghai Scientific Technological Innovation Project (No. 13411951200).

以一端连有单电子转移自由基聚合(RAFT)链转移剂的聚乙二醇(PEG)为大分子链转移剂, 调控2-(4-羟基丁酰氧基)甲基丙烯酸叔丁酯(tBHBMA)的RAFT聚合, 得到的PEG-b-PtBHBMA嵌段共聚物引发丙交酯的开环聚合, 制得接枝共聚物PEG-b-(PtBA-g-PLA). 通过聚乳酸末端的羟基与7-甲氧基香豆素- 3-羧酸(COU)中羧基的酯化反应, 得到了含有荧光标记分子的接枝共聚物PEG-b-(PtBA-g-PLA-COU). 该聚合物主链选择性水解, 得到了含有荧光标记分子的两亲性接枝共聚物PEG-b-(PAA-g-PLA-COU). 以PEG-b-(PAA-g-PLA-COU)为药物载体, 对阿霉素(DOX)进行了负载, 制得了含有荧光标记分子的聚合物载药胶束. 利用紫外光谱和动态光散射测定了载药胶束的载药量和胶束尺寸.

关键词: 接枝共聚物, 聚合物载药胶束, 香豆素, 阿霉素

The end of linear m-PEG-OH was functionalized to provide m-PEG-CTA macro-RAFT agent. RAFT homopolymerization of tBHBMA was conducted to give PEG-b-PtBHBMA diblock copolymer, which initiated ROP of lactide directly. The obtained graft copolymer, PEG-b-(PtBA-g-PLA), was then esterified with 7-methoxycoumarin-3- carboxylic acid to afford PEG-b-(PtBA-g-PLA-COU) containing fluorescent dye molecule. PEG-b-(PAA-g-PLA-COU) amphiphilic graft copolymer was prepared by selective hydrolysis of PtBA segment. Finally, doxorubicin (DOX) was loaded into polymeric micelles aggregated by PEG-b-(PAA-g-PLA-COU). The drug loading content (DLC) and size of the obtained polymeric drug micelles containing fluorescent dye molecule was measured by UV-vis and DLS.

Key words: graft copolymer, polymeric drug micelles, coumarin, doxorubicin