Mitochondria-targeted curcumin microneedles for psoriasis therapy via autophagy activation and epidermal hyperplasia suppression.

Psoriasis is a chronic inflammatory skin condition that features abnormal hyperplasia of keratinocytes, immune dysregulation, and excessive inflammation. It has been demonstrated that curcumin (Cur) presents therapeutic benefits for psoriasis. Nevertheless, the clinical potential of Cur has been limited by its inadequate solubility and relatively poor stability within the physiological environment in vivo. To address these limitations, we synthesized a mitochondria-targeted Cur derivative (Cur-TPP) through conjugation with 4-carboxybutyltriphenylphosphonium bromide, which significantly improved physicochemical physiological stability. Cur-TPP was encapsulated into micelles and integrated into dissolvable microneedles (Cur-TPP@Mil MNs), effectively extending the retention of Cur in the skin (over 24 h). In an imiquimod-induced psoriatic mouse model, treatment with Cur-TPP@Mil MNs for 10 days reduced epidermal hyperplasia by 70% and significantly decreased Ki67-positive keratinocyte proliferation. Moreover, the treatment restored immune homeostasis, with approximately 60% reduction in IL-17A and about 40% decrease in TNF-α levels in lesional skin. Overall, Cur-TPP@Mil MNs exhibit promising potential in the treatment of psoriasis by alleviating epidermal hyperplasia and restoring microenvironmental homeostasis.