Celastrol-loaded metal-phenolic nanozymes integrated microneedles with ROS scavenging and anti-inflammatory activities for psoriasis treatment

Psoriasis is a chronic inflammatory skin disease, which seriously affects the physical and mental health of patients. The progression of psoriasis is influenced by the excessive production of reactive oxygen species (ROS) and inflammatory responses. In this paper, novel celastrol (Ce)-loaded metal-phenolic nanozymes (tannic acid-Fe3+) (TA-Fe) integrated microneedles (Ce@TA-Fe/MNs) were constructed to achieve the combined oxidative stress alleviation and anti-inflammatory therapy of psoriasis. Molecular dynamics simulations and structural characterization confirmed the successful fabrication of nanozymes. The Ce@TA-Fe/MNs system, characterized by its rapid dissolution kinetics and superior mechanical strength, enabled minimally invasive skin penetration for efficient nanozymes delivery. Nanozymes possessed superoxide dismutase and catalase mimetic enzyme activities, effectively eliminating excessive ROS in psoriatic skin lesions. Additionally, the release of Ce from Ce@TA-Fe provided strong antioxidant and anti-inflammatory effects. Based on these characteristics, Ce@TA-Fe/MNs could effectively alleviate the symptoms in psoriasis mice models. These findings demonstrated that the integration of Ce-equipped nanozymes within MNs holds great promise as a therapeutic strategy for the clinical management of psoriasis.