化学学报 ›› 2015, Vol. 73 ›› Issue (5): 416-422.DOI: 10.6023/A15010060 上一篇    下一篇

研究论文

pH敏感型聚合物PEG-b-PHEMA(His)的合成及胶束性能研究

胡齐, 李玉祥, 王静媛, 李亚鹏   

  1. 吉林大学化学学院 麦克德尔米德实验室 长春 130012
  • 收稿日期:2015-01-22 出版日期:2015-05-14 发布日期:2015-03-10
  • 通讯作者: 李亚鹏 E-mail:maishilou134@163.com
  • 基金资助:

    项目受国家自然科学基金(No. 20904014)资助.

Synthetic of pH-Sensitive PEG-b-PHEMA(His) Polymers andthe Study of Micelle

Hu Qi, Li Yuxiang, Wang Jingyuan, Li Yapeng   

  1. College of Chemistry, Jilin University, Alan G. MacDiarmid Institute, Changchun 130012
  • Received:2015-01-22 Online:2015-05-14 Published:2015-03-10
  • Supported by:

    Project supported by The National Natural Science Foundation of China (No. 20904014).

通过点击化学(Click chemistry)与原子转移自由基聚合(ATRP)一锅法合成AB型嵌段聚合物聚乙二醇嵌段聚甲基丙烯酸羟乙酯(PEG-b-PHEMA), 之后对所得聚合物进行组氨酸(His)修饰得到pH敏感型聚合物PEG-b-PHEMA(His), 运用核磁共振(1H NMR)及凝胶渗透色谱(GPC)表征了该嵌段聚合物及组氨酸修饰后的产物的结构和分子量分布(Mn= 8.2×103~13.0×103 g/mol, PDI=1.27~1.51), 说明聚合物被成功地合成且具有较小的多分散系数. 之后对嵌段聚合物PEG-b-PHEMA(His)进行了动态光散射(DLS)、透射电镜(TEM)和临界胶束浓度(CMC)的测试, 结果表明, 聚合物胶束呈球形且粒径分布均匀, 并且粒径随组氨酸接枝率增大而减小. 最后我们做不同接枝比的PEG-b-PHEMA(His)的酸碱滴定曲线, 结果表明, 组氨酸的接入使聚合物具备明显的pH响应能力, 进一步的释药试验也证明了这一结果.

关键词: 一锅法, 组氨酸, pH敏胶束

One-pot reaction strategy has been widely used in the synthesis of different polymer architectures which accelerates synthetic procedure and reduces the number of reactions as well as purification steps, therefore leading to more environmentfriendly products. Imidazole group of histidine (His) can exhibit proton sponge effect at different pH values. We design a polymer micelles with histidine to achieve the pH response capability. Synthesis of (PEG-b-poly-hydroxyethyl methacrylate) PEG-b-PHEMA block copolymer combined click chemistry and atom transfer radical polymerization by one-pot syntheses strategy, then through esterification reaction graft histidine on the polymer side chain to get (polyethylene glycol- b-poly-hydroxyethyl methacrylate-g-histidine) PEG-b-PHEMA(His). The reactions are controllable, and the structure of obtained copolymer is well characterized. PEG-b-PHEMA, PEG-b-PHEMA(His)'s structures were characterized by 1H NMR and GPC tests. The resulting data shown by GPC to give the exact molecular weight and narrow distribution. Mn=8.2×103~13.0×103 g/mol, PDI=1.27~1.51. After the preparation of pH-sensitive drug copolymer micelles in borate buffer solution, the dynamic light scattering (DLS) test was done to test the particle size of the micelles. Then we used fluorescence spectroscopy to test its critical micelle concentration. The micelle diameter increases and the critical micelle concentration gradually reduces as the histidine graft ratio increase. Transmission electron microscopy (TEM) tests showed that the polymer micelle is spherical and narrow particle size distribution and the conclusion is consistent with the DLS test. Also, the acid-base titration and medicine released experiments curves proved that the product micelles have the ability of pH-sensitive response. The embedding of anticancer drug doxorubicin (DOX) was achieved by phase transfer method to get PEG-b-PHEMA(His)@DOX. The drug release rate was measured by counting the optical density (OD) value. The result shows that the release rate of DOX increased from 10% to 40%, thus demonstrating that the PEG-b-PHEMA(His) DOX system has a pH-sensitive response capability. Such micelles can be used as drug carriers for biomedical applications.

Key words: one-pot reaction, histidine, pH-sensitive micelle