高等学校化学学报 ›› 2020, Vol. 41 ›› Issue (12): 2822-2831.doi: 10.7503/cjcu20200378

• 高分子化学 • 上一篇    下一篇

温度/pH响应性MPEG-b-PCL/PNVCL-b-PCL共聚物复合胶束的制备及载药性质

张萌, 王绍森, 辛宇豪, 刘学, 吴秋华(), 张国林()   

  1. 辽宁大学化学院, 沈阳 110036
  • 收稿日期:2020-06-22 出版日期:2020-12-10 发布日期:2020-12-09
  • 通讯作者: 吴秋华,张国林 E-mail:wuqiuhua@lnu.edu.cn;glzhang@lnu.edu.cn
  • 基金资助:
    国家自然科学基金(51373073);辽宁省自然科学基金(批准号(2019-ZD-0192);20180550947)资助

Preparation and Drug Delivery Properties of Thermo/pH Dual Responsive Copolymer Composite Micelles of MPEG-b-PCL/PNVCL-b-PCL

ZHANG Meng, WANG Shaosen, XIN Yuhao, LIU Xue, WU Qiuhua(), ZHANG Guolin()   

  1. College of Chemistry,Liaoning University,Shenyang 110036,China
  • Received:2020-06-22 Online:2020-12-10 Published:2020-12-09
  • Contact: WU Qiuhua,ZHANG Guolin E-mail:wuqiuhua@lnu.edu.cn;glzhang@lnu.edu.cn
  • Supported by:
    ? Supported by the National Natural Science Foundation of China(51373073);the Natural Science Foundation of Liaoning Province of China(2019?ZD?0192)

摘要:

以基于亚胺键的嵌段共聚物为构筑单元的温度/pH响应性共聚物复合胶束(CMs), 由于具有亚胺键和核-壳-冠结构, 表现出较高的灵敏度和稳定性. 以聚乙二醇单甲醚(MPEG)、 N-乙烯基己内酰胺(NVCL)和ε-己内酯(ε-CL)为原料, 分别制备了端醛基聚乙二醇单甲醚(MPEG-CHO)、 端醛基聚N-乙烯基己内酰胺(PNVCL-CHO)和端氨基聚己内酯(H2N-PCL), 利用希夫碱反应, 进一步制备了基于亚胺键的聚乙二醇单甲醚-b-聚己内酯(MPEG-b-PCL)和聚N-乙烯基己内酰胺-b-聚己内酯(PNVCL-b-PCL)嵌段共聚物, 对共聚物结构进行了确认. 以MPEG-b-PCL和PNVCL-b-PCL为构筑单元, 制备了共聚物复合胶束, 研究了复合胶束对阿霉素的包载、 释放性质和细胞毒性等. 研究结果表明, 室温下MPEG-b-PCL和PNVCL-b-PCL能够在水中自组装形成以PCL为核、 MPEG和PNVCL为混合壳的共聚物复合胶束, 在生理温度下, 温敏性PNVCL链段发生相变塌缩在PCL核表面, 能够防止药物扩散释放, 亲水性MPEG链段形成可控通道. 药物体外释放结果表明, 在弱酸性环境中, 亚胺键能够断裂, 胶束被破坏, 促进药物的释放, 噻唑蓝(MTT)实验表明, 复合胶束的细胞毒性较低.

关键词: 温度/pH响应, 亚胺键, 共聚物复合胶束, 载药

Abstract:

Thermo/pH dual responsive copolymer composite micelles(CMs) based on the block copolymers with imine bonds show higher sensitivity and stability due to their imine linkage and core-shell-crown three la-yer structure. Using polyethylene glycol monomethyl ether(MPEG), N-vinyl caprolactam(NVCL) and ε-caprolactone(ε-CL) as raw materials, the aldehyde-terminated poly(ethylene glycol) monomethyl ether(MPEG-CHO), aldehyde-terminated poly(N-vinylcaprolactam)(PNVCL-CHO) and amino-terminated polycaprolactone(H2N-PCL) were prepared respectively. Block copolymers, poly(ethylene glycol) monomethyl ether-b-poly(ε-caprolactone)(MPEG-b-PCL) and poly(N-vinylcaprolactam)-b-poly(ε-caprolactone) (PNVCL-b-PCL) based on imine bond, were synthesized by reaction of H2N-PCL with MPEG-CHO and PNVCL-CHO. At room temperature, MPEG-b-PCL and PNVCL-b-PCL self-assembled to form CMs with PCL as the core and MPEG/PNVCL as the mixed shell in water. At the physiological temperature, thermo-responsive PNVCL collapsed on the PCL core, while MPEG still stretched to form core-shell-corona micelles, which might protect the drug encapsulated in the core. Studies on the in vitro drug release showed that a much faster release rate was observed at slightly acidic media, due to the disruption of imine bonds. 3-(4,5)-Dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide(MTT) assay demonstrated the low cytotoxicity of the composite micelles.

Key words: Temperature/pH response, Imine bond, Copolymer composite micelle, Drug loading

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