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化学进展 2019, Vol. 31 Issue (12): 1653-1668 DOI: 10.7536/PC190327 前一篇   后一篇

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智能响应型水凝胶药物控释体系及其应用

蔡紫煊, 张斌, 姜丽阳, 李允译, 许国贺**(), 马晶军   

  1. 河北农业大学理工学院 沧州 061100
  • 收稿日期:2019-03-25 出版日期:2019-12-15 发布日期:2019-10-15
  • 通讯作者: 许国贺
  • 基金资助:
    河北省高等学校青年拔尖人才计划项目(BJ201702); 河北农业大学引进博士专项(ZD2016027); 河北省大学生创新创业训练计划项目(201810086063); 河北农业大学渤海校区师生协同创新项目(2018bssxt11)
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Intelligent-Responsive Hydrogels-Based Controlled Drug Release Systems and Its Applications

Zixuan Cai, Bin Zhang, Liyang Jiang, Yunyi Li, Guohe Xu**(), Jingjun Ma   

  1. College of Science and Engineering, Agricultural University of Hebei, Cangzhou 061100, China
  • Received:2019-03-25 Online:2019-12-15 Published:2019-10-15
  • Contact: Guohe Xu
  • About author:
    ** E-mail:
  • Supported by:
    Young Tip-top Talents Plan of Universities and Colleges in Hebei Province of China(BJ201702); Specific Foundation for Doctor in Hebei Agriculture University of China(ZD2016027); Undergraduate Innovation and Entrepreneurship Training Program Project of Hebei Province(201810086063); Collaborative Innovation Projects between Teachers and Students of Bohai Campus of Hebei Agricultural University(2018bssxt11)

药物控释体系可改善药物分子在机体内的释放、吸收、代谢和排泄过程,显著提高药物利用率并减弱药物的毒副作用。智能响应型水凝胶凭借其刺激响应性、亲水性和无毒性在药物控释方面得到了广泛的关注。本文介绍了智能响应型水凝胶药物控释体系的概念、机理和应用,详细归纳了智能响应型水凝胶药物控释体系的研究进展。按照刺激源不同将智能响应型水凝胶药物控释体系分为pH响应型、温度响应型、光响应型、生物分子(如葡萄糖、酶)响应型、外场(如电场、磁场)响应型、压力响应型、氧化还原响应型及多重响应型水凝胶药物控释体系。进一步介绍了智能响应型水凝胶药物控释体系在治疗癌症、急性肾损伤、眼病、糖尿病等疾病及抗菌、防止伤口感染等方面的应用。最后,基于目前智能响应型水凝胶药物控释体系存在的一些问题(如生物相容性差、存在突释或滞释现象、不可降解等)对其发展做出了展望。

关键词： 水凝胶, 药物控释体系, 智能响应型

Controlled drug release systems can ameliorate the release, absorption, metabolism and excretion of drug molecules in the body, significantly improve drug utilization and reduce the side effects of drugs. Intelligent-responsive hydrogels have been extensively studied for controlled drug release carriers due to their responsiveness, hydrophilicity, good biocompatibility and non-toxicity. In this paper, the research progress of the intelligent-responsive hydrogels-based controlled drug release systems is summarized in detail, including the conception, mechanism and applications. According to the kinds of external stimuli, the intelligent-responsive hydrogels-based controlled drug release systems can be classified into pH-responsive, temperature-responsive, light-responsive, glucose-responsive, enzyme-responsive, electric field-responsive, magnetic field-responsive, pressure-responsive, redox-responsive and multiple-responsive hydrogels-based controlled drug release systems. The applications of the intelligent-responsive hydrogels-based controlled drug release systems in treating diseases, such as cancer, acute kidney injury, eye diseases, diabetes and its complications, and antibiotic treatments for preventing wound infection are further briefly described. Then, the problems of the intelligent-responsive hydrogels-based controlled drug release systems researches, such as poor biocompatibility, burst release or stagnant release, and non-degradability, are analyzed. Finally, the future development of the intelligent-responsive hydrogel-based controlled drug release systems is prospected.

Key words: hydrogels, controlled drug release systems, intelligent-responsive
()
图1 智能响应型水凝胶药物控释体系溶胀释药机理
Fig. 1 Mechanism of intelligent-responsive hydrogels-based controlled drug release systems through swelling
图2 智能响应型水凝胶药物控释体系收缩释药机理
Fig. 2 Mechanism of intelligent-responsive hydrogels-based controlled drug release systems through shrinking
图3 智能响应型水凝胶药物控释体系降解释药机理[32]
Fig. 3 Mechanism of intelligent-responsive hydrogels-based controlled drug release systems through degradation[32]
图4 阴离子型pH响应型水凝胶药物控释体系释药机理[40]
Fig. 4 Mechanism of anionic pH-responsive hydrogels-based controlled drug release systems[40]
图5 负热敏型水凝胶药物控释体系释药机理
Fig. 5 Mechanism of negative thermosensitive hydrogels-based controlled drug release systems
图6 (a) PEG/PPG/PCL三元共聚物结构及示意图;(b) PEG/PPG/PCL热敏型水凝胶药物控释体系示意图[58]
Fig. 6 (a) PEG/PPG/PCL terpolymer structure and schematic;(b) Schematic diagram of PEG/PPG/PCL thermosensitive hydrogels-based controlled drug release systems[58]
图7 可见光触发释放布洛芬[71]
Fig. 7 The release of ibuprofen driven by visible light[71]
图8 基于β-环糊精-偶氮苯水凝胶的紫外光响应型药物控释体系[72]
Fig. 8 UV-responsive hydrogels-based controlled drug release systems based on β-cyclodextrin-azobenzene[72]
图9 基于PDANPs/4-arm-PEG-SH水凝胶的近红外光响应型药物控释体系[73]
Fig. 9 NIR-responsive hydrogels-based controlled drug release systems based on PDANPs/ 4-arm-PEG-SH[73]
图10 GOD催化葡萄糖转化为葡萄糖酸[14]
Fig. 10 Converting glucose into gluconic acid catalyzed by GOD[14]
图11 (a) MMP-9触发两亲肽可注射水凝胶结构转变释药示意图;(b) 酶响应型可注射水凝胶对癌细胞的杀灭作用示意图[77]
Fig. 11 (a) Schematic diagram of MMP-9 triggering amphiphilic peptide injectable hydrogel structure conversion release;(b) Schematic diagram of the killing effect of enzyme-responsive injectable hydrogel on cancer cells[77]
图12 磁场响应型水凝胶药物控释体系
Fig. 12 Magnetic field-responsive hydrogels-based controlled drug release systems
图13 基于Al-CD的压力响应型药物控释体系[91]
Fig. 13 Pressure-responsive hydrogels-based controlled drug release systems based on Al-CD[91]
图14 基于HRP传递的硫醇聚合物的交互链接[93]
Fig. 14 The scheme of the HRP-mediated cross-linking of the thiolated polymer[93]
图15 基于TKNs水凝胶的氧化还原响应型药物控释体系[94]
Fig. 15 Redox-responsive hydrogels-based controlled drug release systems based on TKNs[94]
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