Frozen-microneedles with novel cerium dioxide nanocomposites for effective relief of irritant contact dermatitis.

Irritant contact dermatitis (ICD), characterized by compromised skin barrier and dysregulated innate immunity, poses significant clinical challenges due to systemic side effects during conventional glucocorticoid-dependent therapies. As a key issue in ICD progression, excessive reactive oxygen species (ROS) cause an increase in the levels of pro-inflammatory factors (IL-6/TNF-α) and the persistent inflammatory microenvironment seriously retarded the recovery of damaged areas of the skin. Herein, we propose a frozen microneedle (FMN)-based delivery system integrating cerium dioxide-chlorophyllin nanocomposites (SSCe NPs) for ICD management. The FMN with SSCe NPs (SSCe-FMN) exhibited superior ROS scavenging efficiency, attributed to the interfacial electron transfer between sodium copper chlorophyllin and Ce³⁺/Ce⁴⁺ redox cycles, which synergistically promotes oxygen vacancy-mediated catalytic ROS decomposition while preventing surface passivation via chlorophyllin chelation. On the murine-based ICD models, SSCe-FMN transdermal delivery achieved notable reduction in inflammatory cytokines (IL-6/TNF-α) within 6 days, accompanied by significantly decreased number of inflammatory cells and mast cells. This work not only demonstrated a novel FMN-enabled ICD therapeutic platform but also attempted to establish a biomimetic antioxidant paradigm leveraging metal-polyphyrin coordination chemistry for treatment of inflammatory skin disorders.