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皮肤的“纳米护盾”水凝胶:杨梅素月桂酸酯纳米制剂的共递送可消除真菌并促进皮肤再生。

Skin's 'nano-shield' hydrogel: Co-delivery of myricetin-laurate nanoagents eliminates fungus and promotes skin regeneration.

作者信息

Zhang Lei, Liu Kailai, Zhou Jiachen, Zhang Yuchen, Wen Jinpeng, He Jiangchuan, Zheng Yunhe, Yang Li, Wang Ke, Tian Jun

机构信息

Department of Dermatology and Venerology, Shaanxi Provincial People's Hospital, Xi'an, China.

School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, China.

出版信息

Bioact Mater. 2025 Jun 25;52:687-701. doi: 10.1016/j.bioactmat.2025.06.027. eCollection 2025 Oct.

DOI:10.1016/j.bioactmat.2025.06.027
PMID:40641579
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12241814/
Abstract

Cutaneous fungal infections, particularly those caused by , pose significant clinical challenges due to high recurrence rates and rising antifungal resistance. Conventional therapies, including azoles and polyenes, are limited by toxicity, resistance, and cost. This study addresses these limitations by developing a multifunctional hydrogel integrating lauric acid (LA)-a natural antifungal anionic surfactant-with the antioxidant plant polyphenol myricetin (Myr). The synergistic combination of LA and Myr disrupts fungal membrane integrity through lipid bilayer destabilization. To enhance therapeutic delivery, myricetin laurate ester was encapsulated in DSPE-PEG2000 micelles and embedded into a hydrogel matrix formed by crosslinking oxidized chondroitin sulfate and hydrazide-functionalized PEG. The resulting hydrogel demonstrated potent antifungal activity against by disrupting cell membranes and alleviating oxidative stress in infected wounds. assays confirmed minimal cytotoxicity to mammalian cells, while in vivo studies in ICR mice showed accelerated healing of -infected skin lesions. The hydrogel's sustained release profile and biocompatibility highlight its potential as a dual-action therapeutic platform, combining antifungal efficacy with antioxidant wound repair. This innovative strategy offers a promising solution to overcome drug resistance, reduce toxicity, and improve outcomes in managing cutaneous candidiasis and related dermatomycoses.

摘要

皮肤真菌感染,尤其是由[具体真菌名称未给出]引起的感染,由于高复发率和不断上升的抗真菌耐药性,带来了重大的临床挑战。包括唑类和多烯类在内的传统疗法受到毒性、耐药性和成本的限制。本研究通过开发一种多功能水凝胶来解决这些局限性,该水凝胶将月桂酸(LA)——一种天然抗真菌阴离子表面活性剂——与抗氧化植物多酚杨梅素(Myr)整合在一起。LA和Myr的协同组合通过破坏脂质双层稳定性来破坏真菌膜的完整性。为了增强治疗递送效果,将月桂酸杨梅素酯包裹在DSPE-PEG2000胶束中,并嵌入由氧化硫酸软骨素和酰肼功能化PEG交联形成的水凝胶基质中。所得水凝胶通过破坏细胞膜和减轻感染伤口中的氧化应激而对[具体真菌名称未给出]表现出强大的抗真菌活性。细胞毒性试验证实对哺乳动物细胞的细胞毒性极小,而在ICR小鼠中的体内研究表明,感染[具体真菌名称未给出]的皮肤损伤愈合加速。水凝胶的缓释特性和生物相容性突出了其作为双作用治疗平台的潜力,将抗真菌功效与抗氧化伤口修复相结合。这种创新策略为克服耐药性、降低毒性以及改善皮肤念珠菌病和相关皮肤真菌病的治疗效果提供了一个有前景的解决方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a1e/12241814/2de21f53841f/gr8.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a1e/12241814/fc1acc88786d/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a1e/12241814/2de21f53841f/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a1e/12241814/f16c6da5cf50/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a1e/12241814/b3a87670d9cd/sc1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a1e/12241814/d90ea0bcf3dc/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a1e/12241814/a9c0127872b3/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a1e/12241814/6b9b69e37b08/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a1e/12241814/b114e175aeae/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a1e/12241814/ba3d40e56347/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a1e/12241814/ebecbbb56349/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a1e/12241814/fc1acc88786d/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a1e/12241814/2de21f53841f/gr8.jpg

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本文引用的文献

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Cutaneous Fungal Infections Caused by Dermatophytes and Non-Dermatophytes: An Updated Comprehensive Review of Epidemiology, Clinical Presentations, and Diagnostic Testing.皮肤癣菌和非皮肤癣菌引起的皮肤真菌感染:流行病学、临床表现及诊断检测的最新综合综述
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