pH敏感性生物基纳米载药粒子的研究进展

doi:10.16085/j.issn.1000-6613.2020-1423

摘要/Abstract

摘要：

生物基来源的聚合物具有生物相容性高、无毒易降解等优势，近些年来作为药物载体在生物医药领域受到了广泛的关注。人体内的生理环境存在pH差异，利用pH作为刺激响应的信号，可以赋予聚合物纳米载药系统理想的靶向释药性能。本综述着眼于pH敏感性的生物基聚合物纳米粒子，揭示了纳米载药粒子中化学键断裂与质子化作用两种pH响应的控释机制，并针对两者的控释特点进行了分析总结。在此基础上，介绍了几种生物基药物载体的pH控释研究及其在生物医药领域的应用进展，并提出了目前利用各种生物基材料作为药物载体存在的问题。最后，针对目前存在的载药量低、敏感性不强等问题，提出了可采用多种方式联合载药、多重刺激响应结合等方式进行深入研究的展望。

关键词: pH敏感性, 生物基, 聚合物纳米粒子, 载药, 控释机制

Abstract:

In recent years, bio-based polymers with the advantages of high biocompatibility, non-toxic and easily degradable, have attracted extensive attention as drug carriers in the field of biomedicine. Due to pH differences of the physiological environment in human body, the response to pH signal stimulus can endow the polymer nano drug delivery system with ideal targeted drug release performance. This review focuses on pH-sensitive bio-based polymer nanoparticle drug delivery system, reveals two pH controlled release mechanisms of chemical bond cleavage and protonation in nano drug delivery systems, and analyzes the two controlled release characteristics. On this basis, the research on pH controlled release of several natural macromolecular materials as drug carriers and the latest research progress in their use in the field of biomedicine are discussed, and the current problems of using various natural macromolecules as drug carriers are pointed out. Finally, in view of the current problems of low drug loading and low sensitivity, it is suggested that in-depth research can be carried out by combining drug loading and multiple stimulus response combinations.

Key words: pH-sensitive, bio-based, polymer nanoparticle, drug delivery, controlled release mechanism

中图分类号:

TQ460

易聪华, 徐青荷, 王淼, 杨东杰. pH敏感性生物基纳米载药粒子的研究进展[J]. 化工进展, 2021, 40(6): 3411-3420.

YI Conghua, XU Qinghe, WANG Miao, YANG Dongjie. Research progress of pH-sensitive biopolymer nanocarriers[J]. Chemical Industry and Engineering Progress, 2021, 40(6): 3411-3420.

图/表 9

参考文献 62

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类型	pH敏感范围	化学结构	降解产物
腙键（hydrazone）	5.0
β-羧基酰胺键（amide）	4.5~6.0
亚胺键（imine）	6.8

类型	pH敏感范围	化学结构	降解产物
腙键（hydrazone）	5.0
β-羧基酰胺键（amide）	4.5~6.0
亚胺键（imine）	6.8

类型	pH敏感值	化学结构	质子化/ 离子化作用
咪唑基（imidazole）	6.5
氨基（amino）	约6.5
叔氨基（tertiary amino）	约6.5
羧基（carboxyl）	约7.4

类型	pH敏感值	化学结构	质子化/ 离子化作用
咪唑基（imidazole）	6.5
氨基（amino）	约6.5
叔氨基（tertiary amino）	约6.5
羧基（carboxyl）	约7.4

聚合物骨架	药物	pH敏感化学键/基团	负载率/%	封装率/%	应用方向	参考文献
光交联壳聚糖-香豆素	槲皮素	亚胺键	10.2	78.4	肿瘤化疗	［35］
壳聚糖/硫酸葡聚糖/壳聚糖	紫杉醇和5-氟尿嘧啶	氨基	—	66.3、75.2	肿瘤化疗	［30］
羧甲基壳聚糖	阿霉素	氨基和羧基	53.02	16.77	肿瘤化疗	［31］
聚乙二醇化羧甲基壳聚糖	阿霉素	叔氨基、氨基和羧基	>36	—	肿瘤化疗	［32］
海藻酸-精氨酸-壳聚糖	吡喹酮或伊维菌素	氨基和羧基	—	—	口服给药	［33］
海藻酸-壳聚糖	甲苯达唑或伊维菌素	氨基和羧基	—	—	口服抗寄生虫给药	［34］