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基于超吸水性壳聚糖的水凝胶海绵作为卡泊芬净抗真菌药物的载体。

Super absorbent chitosan-based hydrogel sponges as carriers for caspofungin antifungal drug.

机构信息

Laboratory of Polymer Chemistry and Technology, Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Department of Physics, Aristotle University of Thessaloniki, GR54124 Thessaloniki, Greece.

出版信息

Int J Pharm. 2021 Sep 5;606:120925. doi: 10.1016/j.ijpharm.2021.120925. Epub 2021 Jul 23.

Abstract

Novel chitosan copolymers (CS-g-SBMA) grafted with [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (SBMA) in various molar ratio 1.5:1, 5:1, 11.5:1 and 20:1, were synthesized in the present study. SBMA was selected as zwitterion molecule showing promising antibacterial properties. Grafted chitosan derivatives were fully characterized for their successful synthesis by NMR and FT-IR, for their crystallinity by XRD showing reduced crystallinity compared to CS alone. Furthermore, swelling studies were conducted with the grafted derivatives showing extensive swelling capacity (maximum degree of swelling up to 1800%) and water absorption was studied with differential scanning calorimetry and equilibrium water adsorption/desorption isotherms were analyzed. Caspofungin, a novel antifungal drug, was used to prepare a double-acting system, with both antibacterial and antifungal properties, proper for topical use. Drug loaded hydrogels were prepared with 10, 20 and 30 wt% drug content and the loaded hydrogels were fully characterized while antimicrobial studies showed enhanced properties. Caspofungin in vitro release showed an initial burst effect followed by a diffusion process while data analysis verified the initial burst release followed by a quasi Fickian diffusion-driven sustained release. Enhance antimicrobial properties was also observed in caspofungin-loaded hydrogels showing the successful fulfill of our scope; an amphiphilic system having great potential for the development of patches with inherent antimicrobial properties and prolonged antifungal properties.

摘要

本研究合成了不同摩尔比(1.5:1、5:1、11.5:1 和 20:1)接枝[2-(甲基丙烯酰氧基)乙基]二甲基-(3-磺丙基)氢氧化铵(SBMA)的新型壳聚糖共聚物(CS-g-SBMA)。SBMA 是一种两性离子分子,具有有前景的抗菌性能。通过 NMR 和 FT-IR 对接枝壳聚糖衍生物进行了充分的表征,以证明其成功合成,通过 XRD 表明其结晶度与单独的 CS 相比有所降低。此外,还进行了接枝衍生物的溶胀研究,显示出广泛的溶胀能力(最大溶胀度高达 1800%),并通过差示扫描量热法研究了水吸收,分析了平衡水吸附/解吸等温线。两性霉素 B 是一种新型抗真菌药物,用于制备具有抗菌和抗真菌双重作用的双效系统,适合局部使用。用 10、20 和 30 wt%的药物含量制备载药水凝胶,并对载药水凝胶进行了充分的表征,同时抗菌研究显示出增强的性能。两性霉素 B 的体外释放显示出初始突释效应,随后是扩散过程,而数据分析验证了初始突释释放后是准菲克扩散驱动的持续释放。在载有两性霉素 B 的水凝胶中也观察到了增强的抗菌性能,这表明我们的目标得到了成功实现;一种具有很大潜力的两亲性系统,可用于开发具有内在抗菌性能和延长抗真菌性能的贴剂。

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