Sprayable Integrated Hydrogel for Synergistic Alleviation of Oxidative Stress in Atopic Dermatitis Treatment

Abstract Atopic dermatitis (AD) is a chronic inflammatory skin disorder whose pathogenesis is primarily associated with impaired skin barrier function and abnormal immune responses. Oxidative stress is a key factor exacerbating inflammation and itching. To address the challenge that existing local therapies struggle to sustainably regulate redox balance in the microenvironment, this study cross-linked carboxymethylated housefly chitosan (CMCS) with oxidized fucoidan (OFUA) to form an imine-linked hydrogel (C/O) via a Schiff base reaction and loaded it with a functionalized nanoparticle. This nanoparticle was a cyclodextrin metal–organic framework (P-M@CA) loaded with chlorogenic acid (CA) and surface-modified with polydopamine (PDA). A composite hydrogel system (C/O/P) for AD treatment was successfully constructed. This system exhibited strong antioxidant activity both in vitro and in vivo and effectively alleviated oxidative stress associated with AD. The C/O/P hydrogel dramatically decreased epidermal thickening, inhibited mast cell infiltration, downregulated the key inflammatory factor thymic stromal lymphopoietin (TSLP), and lowered serum immunoglobulin E (IgE) levels in an AD mouse model established by induction with 1-chloro-2,4-dinitrobenzene (DNCB). In summary, C/O/P hydrogels effectively clear reactive oxygen species and regulate the oxidative stress microenvironment, offering a promising local delivery strategy for AD treatment.