Microsphere-integrated hydrogel microneedle patch for sustained methotrexate delivery in the long-term management of atopic dermatitis

Atopic dermatitis (AD) is a chronic inflammatory skin condition requiring long-term management. Methotrexate (MTX) is an effective treatment for moderate-to-severe AD, but traditional administration methods suffer from low bioavailability, frequent dosing, and side effects. This study presents a microsphere-integrated hydrogel microneedle (MP-HMN) patch for localized and sustained MTX delivery. Fabricated using a two-casting micromolding, this patch consisting of microneedle arrays made from MTX-loaded poly (lactic-co-glycolic acid) microspheres and photo-crosslinked gelatin methacryloyl (GelMA), supported by a hyaluronic acid (HA) backing. The integration of microspheres enhances mechanical strength of microneedles, while crosslinked GelMA minimizes the burst release of MTX. The MP-HMNs penetrates the skin easily and separates from the HA backing as the HA rapidly dissolves on contact with skin interstitial fluid. The implanted MP-HMNs degrades gradually within the skin, allowing for a 12-day release of MTX. In an AD mouse model, this patch demonstrated superior therapeutic efficacy and reduced dosing frequency, compared to oral and subcutaneous MTX administration, offering a promising strategy for long-term management of AD and other chronic skin diseases.