Psoriasis, a prevalent immunoinflammatory skin condition, is characterized by abnormal skin thickening, which complicates traditional topical drug delivery and hinders drug penetration. Our goal is to enhance the efficacy of psoriasis treatment by developing a transdermal drug formulation. Microneedles (MNs) can improve treatment outcomes by increasing the absorption of topical medications through skin penetration. Curcumin (Cur), a natural anti-inflammatory, antioxidant, and immunomodulatory small molecule with water-insoluble properties, shows promise for psoriasis relief. In this research, three Cur nano-formulations (NFs) were screened and prepared using antisolvent and ethanol injection methods, with one being dispersed into hyaluronic acid (HA) dissolving MNs. A transdermal nano-MNs delivery system was constructed using a double-layer centrifugation technique. This co-delivery system overcame Cur's solubility issues, poor absorption, and instability, allowing targeted and efficient delivery of Cur-NFs to the skin without being hindered by the skin barrier. In vitro studies demonstrated that Cur-NF dissolving MNs possess adequate mechanical properties for skin implantation, exhibit rapid dissolution, and achieve an effective drug release rate of 73 % within 6 h. Pharmacodynamic evaluations demonstrated that the MNs system effectively ameliorated key psoriatic skin manifestations. Notably, MNs treatment significantly reduced the Psoriasis Area and Severity Index (PASI) score from 12.0 +/- 0.0 (model group) to 4.7 +/- 0.5 (p < 0.05), alongside a marked suppression of pro-inflammatory cytokines, including TNF-alpha, IL-17, IL-22, and IL-23, compared to untreated psoriatic controls. Therefore, the composite dissolving MNs delivery system loaded with Cur-NFs represents a promising approach for psoriasis treatment.
