Antioxidant Hydrogel-Based Transdermal Drug Delivery Patch for Reactive Oxygen Species- and MyD88-Targeted Management...

Atopic dermatitis (AD) is a chronic inflammatory skin disorder driven by skin barrier dysfunction, immune dysregulation, a self-perpetuating cycle of inflammation and oxidative stress. Current therapies often target either oxidative stress or inflammation, yielding suboptimal outcomes. To overcome this, we developed Ce@iMyD88, a synergistic nanozyme, conjugating mesoporous cerium oxide nanoparticles with a MyD88 inhibitor (iMyD88), engineered to simultaneously scavenge reactive oxygen species (ROS) and suppress MyD88/NF-κB-mediated inflammatory signaling. Encapsulation in a lignin-based hydrogel provided biocompatibility, stability, and intrinsic antioxidant properties. In vitro, Ce@iMyD88 neutralizes superoxide, hydrogen peroxide, hydroxyl radicals, and attenuated ROS/proinflammatory cytokine expression in 2,4-dinitrochlorobenzene (DNCB)/H₂O₂-stimulated HaCaT keratinocytes. In vivo, applications in DNCB-induced AD and H₂O₂-challenged mice reduced epidermal thickness, mast cell infiltration, and restored skin barrier integrity. Compared with monotherapies, Ce@iMyD88 hydrogels markedly alleviated oxidative stress and inhibited MyD88/NF-κB signaling, reducing lesion severity and providing a precise strategy for managing inflammatory skin diseases through integrated nanoscale interventions.