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

Chien-Ju Lin,1 Bang-Yu Wen,2 Yu-Kai Liang,3 Wen-Chen You,4 Hsiu-O Ho,5 Ming-Thau Sheu,6 Hong-Liang Lin,1,7 Ling-Chun Chen2 1School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China; 2Department of Biotechnology and Pharmaceutical Technology, Yuanpei University of Medical Technology, Hsinchu, Taiwan, Republic of China; 3Department of Pharmacy, Chia-Nan University of Pharmacy and Science, Tainan, Taiwan, Republic of China; 4Division of Medical Devices and Cosmetics, Taiwan Food and Drug Administration, Ministry of Health and Welfare, Taipei, Taiwan, Republic of China; 5School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan, Republic of China; 6Panion & BF Biotech Inc., Taipei, Taiwan, Republic of China; 7School of Pharmacy, College of Pharmacy, National Defense Medical University, Taipei, Taiwan, Republic of ChinaCorrespondence: Hong-Liang Lin, Email [email protected] Ling-Chun Chen, Email [email protected]: 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.Keywords: atopic dermatitis, sacchachitin nanofibers, melatonin, hydrogel, NC/Nga mice