A transdermal delivery system using microneedle patches containing poly(lactic-co-glycolic)-encapsulated acitretin nanoparticles for topical and extended treatment

Acitretin is a primary treatment for moderate-to-severe psoriasis, however, the substantial side effects associated with its daily oral administration and relapse after withdrawal significantly restrict its clinical utility. To address this challenge, we designed a transdermal delivery system using hyaluronic acid-based dissolving microneedle patches containing poly (lactic-co-glycolic)-encapsulated acitretin nanoparticles for effective topical drug administration and prolonged therapeutic effects. This microneedle exhibited favorable mechanical properties, which could easily penetrate through the thickened epidermis for intralesional drug delivery. We showed that numbers of acitretin-loaded microspheres were uniformly compacted at the bottom of needle tips, giving the microneedle dense surface morphology required for effective skin penetration, prolonged retention, and sustained release of acitretin both in vitro and in an imiquimod-induced psoriasis in vivo model. A single dose of our transdermal treatment not only alleviated the psoriasis-like skin inflammation in acute phase, but also established a long-term therapeutic effect. Moreover, the transdermal approach proved more effective than daily oral administration of the same dose of free drug, demonstrating less systemic toxicity than oral drug intake or topical cortisol application. This new system offers an innovative way for drug delivery and disease treatment, and also provides an antimicrobial control strategy for a wide range of applications. [Display omitted] •The innovative microneedle patch system containing nanoparticles is effective in treatment of psoriatic lesions.•Superior therapeutic outcomes are demonstrated in an imiquimod-induced psoriasis mouse model.•A single patch application matches the efficacy of multiple doses of traditional treatments.•The patch maintains a favorable safety profile, highlighting its potential as a safe, innovative psoriasis treatment.