Piezoelectric-Driven Microneedle Array Delivery of Methotrexate for Enhanced Psoriasis Treatment

Methotrexate (MTX) is one of the mainstays in the treatment of psoriasis and psoriatic arthritis. However, it is mainly administered orally or by subcutaneous injection, which is not so satisfactory with many side effects. While orally administered MTX may cause gastrointestinal side effects, subcutaneous injection is often painful and may affect patient compliance. To address these limitations, we investigated the minimally invasive transdermal drug delivery strategy, a piezoelectric-driven microneedle array (PDMA) that can efficiently overcome the thickened epidermis and controlled delivery of MTX. PDMA was prepared from piezoelectric ceramic disks and a 3D-printed microneedle array patch. The finite element model was established to validate the ultrasound field generated by PDMA and analyze the relationship between the frequency and amplitude of PDMA penetrating the skin. PDMA demonstrated a satisfactory enhancement of drug permeation and achieved greater depth of delivery of MTX, enhanced 9 times compared with untreated skin in the in vitro study. The in vivo study demonstrates that PDMA-mediated delivery of MTX significantly enhances therapeutic outcomes in alleviating psoriasis symptoms, outperforming oral administration while requiring only 50% of the conventional oral dosage. Therefore, PDMA could be a promising approach for effective and controlled transdermal drug delivery methods of MTX as a potential enhanced treatment for psoriasis.