Preparation of a thermosensitive and antibacterial in situ gel using poloxamer-quaternized chitosan for sustained ocular delivery of Levofloxacin hydrochloride

文献类型： 外文期刊

第一作者： Chen, Zihan

作者： Chen, Zihan;Wang, Anyu;Qin, Yiming;Xiao, Ying;Yu, Xi;Zhong, Tian;Zhang, Kang;Chen, Xu;Zhu, Xiaoming;Feng, Xiao;He, Guangyun

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关键词： In situ gel; Quaternized chitosan; Thermosensitive; Sustained release; Antibacterial

期刊名称：INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES （ 影响因子：8.5； 五年影响因子：8.7 ）

ISSN： 0141-8130

年卷期： 2024 年 283 卷

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收录情况： SCI

摘要： In this study, a thermosensitive in situ gel with porous structure was developed using poloxamer (Po) and N-(2hydroxy-3-trimethyl ammonium) propyl chitosan chloride (HTCC). The poloxamer-quaternized chitosan (PoHTCC) in situ gel exhibited superior rheological property, water absorption capacity and antibacterial activity against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Streptococcus pyogenes, making it wellsuited for ocular applications. Scanning electron microscope revealed a macroporous architecture with pore sizes ranging from 1 to 2 mu m, suggesting that the gel has desirable breathability, corneal adhesion capability, and overall conformability. In vitro drug release assay was conducted with levofloxacin hydrochloride, demonstrating that sustained release over 48 h could be achieved at 34 degrees C, with approximately 80 % of the drug released within this timeframe. Computational simulations revealed substantial binding affinity between the material and the Escherichia coli outer membrane lipopolysaccharide-associated protein and corneal mucin. The protein showing the strongest binding energy to N-(2-hydroxy-3-trimethyl ammonium) propyl chitosan chloride (HTCC), as calculated by the Molecular Mechanics Generalized Born Surface Area Method (MM-GBSA), was LptD-LptE, with a binding energy of -61.14 +/- 4.72 kcal/mol. These results underscore the potential of this system for effective and convenient ocular delivery with sustained drug release.

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