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

Cutaneous fungal infections, particularly those caused by Candida albicans, 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 C. albicans by disrupting cell membranes and alleviating oxidative stress in infected wounds. In vitro assays confirmed minimal cytotoxicity to mammalian cells, while in vivo studies in ICR mice showed accelerated healing of C. albicans-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.