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 tipswellable microneedle array patch (TSMAP) using photo-crosslinked 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.

Swellable Microneedles in Drug Delivery and Diagnostics

“…By offering a user-friendly and efficient alternative for administering methotrexate, this design reduces side effects and improves drug retention at the target site. Such advancements could significantly decrease the overall treatment burden for patients [ 47 ].…”

“…One study demonstrated the fabrication of light-responsive hydrogel-forming microneedle arrays using micromolding capable of delivering ibuprofen upon exposure to light, thus enabling controlled, on-demand drug release [ 9 ]. Another study introduced a tip-swellable microneedle array patch (TSMAP) for the sustained delivery of methotrexate (MTX) in psoriasis treatment using photo-crosslinked methacrylated hyaluronic acid (MeHA) and biocompatible resin, ensuring efficient drug loading and minimal wastage [ 47 ]. Research has also explored hydrogel swelling to trigger the release of biodegradable polymer microneedles, showing sustained drug release and effective delivery of model drugs by micromolding poly-lactic-co-glycolic acid (PLGA) after filling the cavities of the mold with hydrogel microparticles [ 82 ].…”

“…Fabrication and Mechanical Integrity: Establishing robust methods for the fabrication of swellable MNs is imperative. Researchers should explore and assess various manufacturing techniques, including 3D printing, micromolding, and injection molding, to identify the best approach for achieving optimal mechanical properties and consistent product quality [ 6 , 9 , 18 , 41 , 46 , 47 , 56 ]. Mechanical strength and skin penetration tests are essential and must be rigorously executed to confirm that the MNs can withstand insertion forces without breaking and are capable of effectively penetrating the skin [ 15 , 16 , 28 , 35 , 36 , 39 , 42 , 44 ].…”

“…Both in vitro and in vivo studies are necessary to evaluate drug release following skin penetration [ 9 , 10 , 11 , 13 , 28 , 38 , 41 , 43 , 46 , 76 ]. Controlled and sustained release studies are particularly vital for chronic disease management, ensuring that drugs are delivered at therapeutic levels over extended periods without the need for frequent reapplication [ 16 , 39 , 41 , 42 , 47 , 52 , 64 ].…”

“…There is a need for improved alignment with physiological conditions, particularly for glucose-responsive applications. Variability in clinical efficacy due to differences in skin types and conditions necessitates further research and tailored solutions [ 27 , 43 , 47 ]. Ensuring the long-term stability and consistent functionality of microneedles across various environments is challenging, particularly in maintaining stability under different storage conditions and integrating them into diverse clinical and personal health scenarios [ 11 , 14 , 33 , 37 , 65 ].…”