咪唑盐类聚离子液体抗菌剂的制备及其在水凝胶敷料中的应用

doi:10.19894/j.issn.1000-0518.200214

摘要/Abstract

摘要： 皮肤伤口的感染严重威胁患者的生命安全,虽然传统的含有银离子或小分子抗生素的抗菌水凝胶伤口敷料具有广谱的杀菌功效,但这些抗菌水凝胶敷料中的抗菌剂存在一定的生物毒性和耐药性风险,无法满足临床长期使用的要求。咪唑盐类聚离子液体由于其含有较强的正电荷效应以及疏水链段,因此其作为新型的聚合物抗菌剂具有较强的抗菌效果。本研究首先通过采用Radziszewski缩聚反应,制备了具有较强抗菌性能的含呋喃官能团的咪唑盐类聚离子液体;其次,将含呋喃官能团的咪唑盐类聚离子液体采用Diels-Alder“点击”反应与透明质酸/聚乙二醇复合,以制备含有咪唑盐类聚离子液体抗菌水凝胶。通过体外实验表明:含咪唑盐类聚离子液体抗菌水凝胶在快速杀灭细菌的同时,对人皮肤的成纤维细胞具有较低的毒性。有望应用在皮肤创面的抗感染及修复领域。

关键词: 抗菌聚合物, 聚离子液体, “点击”反应, 细胞毒性, 水凝胶敷料

Abstract: Skin wound infections seriously threaten the lives of patients. Although traditional antibacterial hydrogels containing biocides such as silver ions or small molecule antibiotics have a broad-spectrum bactericidal effect and are used as wound dressings, the biological toxicity of silver ions and drug resistance of small molecule antibiotics cannot meet the requirements of long-term clinical application. The imidazolium salt-based poly(ionic liquids) are novel polymer antibacterial agents that exhibit strong antibacterial property, owing to their strong positive charge effect and hydrophobic polymer segments. In this study, imidazolium salt-based poly(ionic liquids) contained furan functional groups as strong antibacterial agents were synthesized by Radziszewski reaction. Then, the imidazolium salt-based poly(ionic liquids) were compounded with hyaluronic acid/polyethylene glycol by Diels-Alder “click” reaction to prepare antibacterial hydrogels. The in vitro assays show that the antibacterial hydrogels containing imidazolium salt-based poly(ionic liquids) can quickly kill bacteria and also have low toxicity towards human skin fibroblasts. This kind of hydrogels can be applied in various biomedical fields.

Key words: Antibacterial polymers, Poly(ionic liquids), “Click” reaction, Cytotoxicity, Hydrogel dressin

中图分类号:

O631.5

周超, 生程钜, 闻林林. 咪唑盐类聚离子液体抗菌剂的制备及其在水凝胶敷料中的应用[J]. 应用化学, 2021, 38(1): 51-59.

ZHOU Chao, SHENG Cheng-Ju, WEN Lin-Lin. Preparation of Imidazolium Salt-based Poly(ionic liquids) Antibacterial Agent and Its Application in Hydrogel Dressing[J]. Chinese Journal of Applied Chemistry, 2021, 38(1): 51-59.

参考文献

[1] TUNG N, HUYEN V, CHI S J A, et al. Topical delivery of dexamethasone acetate from hydrogel containing nanostructured liquid carriers and the drug[J]. Arch Pharmacal Res, 2015, 38(11):1999-2007.
[2] HE M, WANG Q, SHI Z, et al. Inflammation-responsive self-regulated drug release from ultrathin hydrogel coating[J]. Colloids Surf B, 2017, 158:518-526.
[3] HOFFMAN A S. Hydrogels for biomedical applications[J]. Adv Drug Delivery Rev, 2002, 54(1):3-12.
[4] ZHAO X, LI P, GUO B, et al. Antibacterial and conductive injectable hydrogels based on quaternized chitosan-graft-polyaniline/oxidized dextran for tissue engineering[J]. Acta Biomater, 2015, 26:236-248.
[5] HUANG W, WANG Y, HUANG Z, et al. On-demand dissolvable self-healing hydrogel based on carboxymethyl chitosan and cellulose nanocrystal for deep partial thickness burn wound healing[J]. ACS Appl Mater Interfaces, 2018, 10(48):41076-41088.
[6] XU Q, ZHENG Z, WANG B, et al. Zinc ion coordinated poly(ionic liquid) antimicrobial membranes for wound healing[J]. ACS Appl Mater Interfaces, 2017, 9(17):14656-14664.
[7] QIN J, GUO J, XU Q, et al. Synthesis of pyrrolidinium-type poly(ionic liquid) membranes for antibacterial applications[J]. ACS Appl Mater Interfaces, 2017, 9(12):11299-11306.
[8] QIAN W, TEXTER J, YAN F. Frontiers in poly(ionic liquid)s:syntheses and applications[J]. Chem Soc Rev, 2017, 46(4):1124-1159.
[9] SAXER S, MARESTIN C, MERCIER R, et al. The multicomponent Debus-Radziszewski reaction in macromolecular chemistry[J]. Polym Chem, 2018, 9(15):1927-1933.
[10] YU F, CAO X, LI Y, et al. Diels-Alder crosslinked HA/PEG hydrogels with high elasticity and fatigue resistance for cell encapsulation and articular cartilage tissue repair[J]. Polym Chem, 2014, 5(17):5116-5123.
[11] CRUZACUNA R, QUIROS M, HUANG S, et al. PEG-4MAL hydrogels for human organoid generation, culture, and in vivo delivery[J]. Nat Protoc, 2018, 13(9):2102-2119.
[12] BADAWY M E I, LOTFY T M R, SHAWIR S M S. Facile synthesis and characterizations of antibacterial and antioxidant of chitosan monoterpene nanoparticles and their applications in preserving minced meat[J]. Int J Biol Macromol, 2020, 156:127-136.
[13] COSTERTON J W, STEWART P S, GREENBERG E P. Bacterial biofilms:a common cause of persistent infections[J]. Science, 1999, 284(5418):1318-1322.