Melatonin-Loaded Sacchachitin Nanofiber Hydrogel as a Novel Non-Steroidal Platform for Atopic Dermatitis Therapy.

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease commonly managed with topical corticosteroids or calcineurin inhibitors, which may raise concerns with long-term use. Safe, non-steroidal topical therapies capable of restoring skin barrier function while modulating local immune responses remain limited. Methods: A sacchachitin nanofiber (SCNF)-based hydrogel incorporating melatonin (MSC) was developed and evaluated for physicochemical properties, stability, and therapeutic efficacy using a 2,4-dinitrochlorobenzene (DNCB)-induced NC/Nga mouse model of AD. Clinical scores, histological features, and immunological biomarkers were assessed. Results: Among the tested formulations, the melatonin-loaded hydrogel (MSC) demonstrated the most pronounced therapeutic efficacy compared with other formulations, significantly reducing AD severity, epidermal hyperplasia, mast cell infiltration, and Th2-associated markers including IgE, IgG1, and IL-4. Melatonin remained chemically stable for at least 31 days and did not compromise hydrogel mechanical or adhesive properties. In this system, sacchachitin nanofibers primarily function as a structural scaffold, whereas melatonin provides the principal biological and immunomodulatory activity. Conclusion: The melatonin-loaded SCNF hydrogel represents a promising non-steroidal and biocompatible topical platform for AD. In this system, SCNF primarily serves as a structural scaffold, whereas melatonin provides immunomodulatory and anti-inflammatory activity. These findings support further translational investigation.