An Esculetin Nanoparticle-Loaded hydrogel system for treating atopic dermatitis

To address the need for topical therapies with enhanced skin penetration and retention for infantile atopic dermatitis (AD), we screened esculetin (Esc), an active monomer from traditional Chinese medicine, in a cellular AD model. Esc demonstrated pronounced anti-inflammatory activity. Subsequently, a self-assembled nanogel delivery system, Esc@(HAP/PSI)-gel, was engineered using hydroxyapatite (HAP) and polysuccinimide (PSI) for sustained release. The optimized nanoparticles were spherical (Average diameter: 156 nm, zeta potential: −15.7 mV) with pH-responsive drug release. Compared with Esc-gel, Esc@(HAP/PSI)-gel significantly enhanced skin permeation and drug retention without inducing irritation. In AD mice, Esc@(HAP/PSI)-gel alleviated skin lesions, reduced ear swelling, lowered the spleen index, attenuated epidermal/dermal thickening, suppressed inflammatory cell infiltration, and modulated key cytokines (IL-6, TNF-α, IgE) more effectively than Esc-gel. Hence, the HAP/PSI-based nanogel delivery system enables the efficient and sustained delivery of Esc, enhances transdermal absorption, and demonstrates considerable therapeutic potential for AD.