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载红霉素纳米液滴的设计、表征及其对抗. 感染性慢性创面的生物学活性

Design, Characterization, and Biological Activities of Erythromycin-Loaded Nanodroplets to Counteract Infected Chronic Wounds Due to .

机构信息

Department of Public Health and Pediatric Sciences, University of Torino, 10126 Turin, Italy.

Department of Life Sciences and Systems Biology, University of Torino, 10126 Turin, Italy.

出版信息

Int J Mol Sci. 2023 Jan 18;24(3):1865. doi: 10.3390/ijms24031865.

Abstract

causes a wide spectrum of diseases varying from mild to life threatening, despite antibiotic treatment. Nanoparticle application could facilitate the foreign pathogen fight by increasing the antimicrobial effectiveness and reducing their adverse effects. Here, we designed and produced erythromycin-loaded chitosan nanodroplets (Ery-NDs), both oxygen-free and oxygen-loaded. All ND formulations were characterized for physico-chemical parameters, drug release kinetics, and tested for biocompatibility with human keratinocytes and for their antibacterial properties or interactions with All tested NDs possessed spherical shape, small average diameter, and positive Z potential. A prolonged Ery release kinetic from Ery-NDs was demonstrated, as well as a favorable biocompatibility on human keratinocytes. Confocal microscopy images showed ND uptake and internalization by starting from 3 h of incubation up to 24 h. According to cell counts, NDs displayed long-term antimicrobial efficacy against streptococci significantly counteracting their proliferation up to 24 h, thanks to the known chitosan antimicrobial properties. Intriguingly, Ery-NDs were generally more effective (10-10 log CFU/mL), than free-erythromycin (10 log CFU/mL), in the direct killing of streptococci, probably due to Ery-NDs adsorption by bacteria and prolonged release kinetics of erythromycin inside cells. Based on these findings, NDs and proper Ery-NDs appear to be the most promising and skin-friendly approaches for the topical treatment of streptococcal skin infections allowing wound healing during hypoxia.

摘要

尽管进行了抗生素治疗,但它仍会导致从轻度到危及生命的广泛疾病。纳米颗粒的应用可以通过提高抗菌效果和减少其副作用来促进对抗外来病原体。在这里,我们设计并生产了载有红霉素的壳聚糖纳米液滴(Ery-ND),包括无氧和含氧两种。所有 ND 制剂均经过物理化学参数、药物释放动力学的特征描述,并进行了与人角质形成细胞的生物相容性测试以及它们的抗菌性能或与链球菌的相互作用测试。所有测试的 ND 都具有球形形状、小的平均直径和正 Z 电位。结果表明,Ery-ND 具有延长的 Ery 释放动力学,并且对人角质形成细胞具有良好的生物相容性。共聚焦显微镜图像显示,ND 从孵育 3 小时开始摄取和内化,直到 24 小时。根据细胞计数,ND 对链球菌表现出长期的抗菌功效,明显抑制其增殖长达 24 小时,这要归功于壳聚糖的已知抗菌特性。有趣的是,与游离红霉素(10 对数 CFU/mL)相比,Ery-ND 通常对链球菌的直接杀伤作用更为有效(10-10 对数 CFU/mL),这可能是由于 Ery-ND 被细菌吸附和红霉素在细胞内的释放动力学延长所致。基于这些发现,ND 和适当的 Ery-ND 似乎是治疗链球菌皮肤感染的最有前途和皮肤友好的方法,允许在缺氧时伤口愈合。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a2e/9915227/6bfa256c0bfa/ijms-24-01865-g001.jpg

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