Intradermal implantation of methotrexate-loaded puerarin-gelatin hydrogel via bubble-generating microneedles for psoriasis treatment

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Methotrexate (MTX) is a primary treatment for moderate to severe psoriasis, but conventional oral or subcutaneous delivery has limitations, including poor drug targeting, side effects, and low patient compliance. This study introduces implantable hydrogel microneedles (HMNs) made from photo-cross-linked gelatin methacryloyl (GelMA) and puerarin (Pue), a traditional Chinese medicine, for intradermal and sustained MTX delivery. The ratio of Pue to GelMA significantly influenced the morphology, mechanical strength, MTX release profiles, and degradation behavior of the HMNs. After insertion into the skin, the backing layer of the microneedles, which incorporates effervescent agents (NaHCO3 and citric acid), rapidly generates gas bubbles (CO₂) upon contact with skin interstitial fluid, facilitating the immediate separation of the HMNs from the backing and their implantation into skin tissue as MTX reservoirs. HMNs with 1.5 % w/v Pue and 20 % w/v GelMA achieved a 10-day MTX release in vivo. In vivo studies demonstrate that MTX-loaded Pue/GelMA HMNs significantly enhance therapeutic outcomes in alleviating psoriasis symptoms and downregulating psoriasis-associated cytokines due to the synergistic effects of MTX and Pue, outperforming oral administration, subcutaneous injection, and GelMA HMNs containing either Pue or MTX alone. This HMN patch offers great promise for improving psoriasis treatment and patient adherence.