Efficient Loading and Sustained Delivery of Methotrexate Using a Tip-Swellable Microneedle Array Patch for Psoriasis Treatment

Abstract

Methotrexate (MTX), a primary treatment for moderate to severe psoriasis, is limited in clinical use due to suboptimal results and severe side effects from subcutaneous (SC) injection and oral administration. Microneedles offer a promising alternative for direct MTX delivery to targeted skin lesions, but issues such as drug wastage, dosage inaccuracy, and limited drug residence time in the lesions remain. This study introduces a tip-swellable microneedle array patch (TSMAP) using photo-cross-linked methacrylated hyaluronic acid (MeHA) and biocompatible resin for effective MTX loading and sustained delivery. A two-cast micromolding with vacuum drying is employed to concentrate cross-linked MeHA in about 30% of the needle's height at the tip, thereby ensuring that only the TSMAP tip swells. Efficient MTX loading into TSMAP tips is achieved through a 30 s drug solution immersion and 10 min drying, potentially minimizing drug waste from incomplete skin insertion due to skin elasticity. The MTX-loaded TSMAP effectively penetrates both porcine and psoriasis-like mouse skin with its tips detaching from the resin substrate and embedding deeply into the skin tissue, thereby functioning as a drug release reservoir. TSMAP significantly prolongs drug retention in skin compared with SC injection and dissolvable microneedles. The in vivo study demonstrates that TSMAP-mediated MTX delivery substantially enhances therapeutic outcomes in alleviating psoriasis symptoms and downregulating psoriasis-associated cytokines, outperforming oral administration, SC injection, and dissolvable microneedles. Thus, TSMAP could offer an efficient and user-friendly alternative for drug administration in the treatment of various skin diseases.

Keywords: hydrogel; methotrexate; psoriasis; sustained release; tip-swellable microneedles.