Dissolving microneedle co-deliver mitochondria-targeted Nanozyme and Tofacitinib for synergistic treatment of Rosacea.

Rosacea is a chronic inflammatory skin disease driven by oxidative stress and inflammation, yet it lacks effective treatments that simultaneously combine antioxidant and anti-inflammatory activities. This scarcity underscores the need for innovative therapeutic strategies. Here, we developed an integrated platform by combining a mitochondria-targeted cerium oxide nanozyme (WTCeNPs) and the JAK inhibitor tofacitinib citrate (Tof) within a dissolving microneedle (MN) system. This formulation is designed to overcome challenges in transdermal delivery and minimize systemic side effects, achieving mitochondrial specificity and efficient skin penetration for enhanced therapeutic efficacy. The synthesized WTCeNPs demonstrated excellent biocompatibility, dual SOD- and CAT-like activities, and mitochondrial-targeting capabilities, enabling the efficient scavenging of reactive oxygen species (ROS). The dissolving microneedles co-loaded with Tof and WTCeNPs (Tof/WTCeNPs-MN) possessed robust mechanical properties, successfully penetrating the stratum corneum and achieving complete drug release within 9 min. In vitro, treatment of LL-37- and HO-induced HaCaT cell models with Tof/WTCeNPs-MN effectively restored intracellular ROS and inflammatory cytokine expression to physiological levels. Furthermore, in vivo studies on an LL-37-induced rosacea model demonstrated that Tof/WTCeNPs-MN significantly ameliorated disease symptoms. Collectively, these findings establish the Tof/WTCeNPs-MN system as a promising, multifunctional therapeutic platform for rosacea.