Localized treatment of oral ulcers via responsive microneedle patch by enhancing mucosal penetration

Oral ulcers are a common and painful condition. Current treatments, including topical corticosteroids like dexamethasone, are hindered by poor drug penetration and systemic side effects. To address these challenges, we developed a dissolving microneedle patch incorporating protease-responsive gelatin nanoparticles encapsulating dexamethasone (DEX@GNPs) for localized delivery to the oral mucosa. This system is engineered to penetrate the mucosal barrier and release dexamethasone in response to the inflammatory microenvironment, thereby enhancing drug deposition at the ulcer site. In a rat buccal ulcer model, the DEX@GNP-loaded microneedles effectively delivered dexamethasone to the target tissue layers, significantly reduced ulcer size and promoted tissue regeneration. Moreover, the responsive release of dexamethasone in the presence of elevated protease levels was associated with a marked reduction in inflammation, as evidenced by decreased levels of key pro-inflammatory cytokines. These findings indicate that DEX@GNP-loaded microneedles provide a promising approach for the localized treatment of oral ulcers and may help to improve therapeutic outcomes by enabling efficient localized corticosteroid delivery.