Hybrid Dissolving Microneedles Incorporating Hyaluronic Acid Microdepots for Pain-free and Long-acting Corticosteroid Therapy.

Inflammatory skin diseases are chronic conditions characterized by persistent inflammation and disrupted skin barriers, necessitating sustained drug delivery. This study presents a long-acting hybrid dissolving microneedle (DMN) patch incorporating hyaluronic acid (HA)-based microparticle depots (TA@MDepots) for intradermal delivery of triamcinolone acetonide (TA). HA is modified to HA acetate to enhance compatibility with hydrophobic TA, enabling efficient microdepot formulation. These TA@MDepots are integrated into the DMN tip layer using mold-casting, resulting in patches with strong mechanical properties and rapid tip dissolution (<3 min) upon application. In vitro and ex vivo studies demonstrate effective skin penetration, sustained dermal retention, and prolonged TA release. The hybrid patch shows excellent cytocompatibility and significantly reduces tumor necrosis factor-alpha and interleukin-6 levels in activated macrophages. In vivo, the patch outperforms commercial TA ointment in a murine ulcer model by accelerating wound closure, reducing epidermal thickening, and lowering inflammatory cytokine expression, despite a lower TA dosage and fewer applications. Histological analyses confirm skin structure restoration and immune modulation, while systemic toxicity assessments show no adverse effects. This hybrid DMN platform offers a minimally invasive, biocompatible, and patient-friendly strategy for prolonged corticosteroid delivery in chronic inflammatory skin diseases and represents a promising alternative to conventional topical or injectable therapies.