Development and preclinical evaluation of a copper-based acidic hydrogel for atopic dermatitis

Atopic dermatitis (AD) features impaired skin barrier, elevated cutaneous pH, and Staphylococcus aureus overcolonization. Restoring acidic skin pH while suppressing microbial overgrowth represents a promising non-steroidal strategy. To develop a copper-based acidic hydrogel and evaluate its properties, antimicrobial activity, efficacy, and safety. A hydrogel with 0.115% copper ions was prepared from basic copper carbonate, acetic acid (6% w/w), and xanthan gum, formulated at a final pH of ∼3.2, and characterized by rheology and stability testing. Antimicrobial activity was evaluated by a quantitative carrier test against S. aureus, E. coli, and C. albicans. Efficacy was assessed in DNFB-induced AD-like BALB/c mice. Dermal safety was examined in a 14-day study in rabbits. The hydrogel showed gel-like behavior (G' > G″) with 94.6% structural recovery and remained stable over 23 months. It achieved >98% killing of all pathogens within 5 min and >99.6% within 10 min. In mice, treatment dose-dependently reduced ear swelling and dermatitis scores, attenuated epidermal hyperplasia, and decreased mast cell infiltration. In rabbits, only mild, reversible local irritation occurred, without systemic toxicity. This copper-based acidic hydrogel exhibits potent broad-spectrum antimicrobial activity, ameliorates AD-like lesions, and shows a favorable short-term dermal safety profile, supporting further development as a non-steroidal topical option for AD.