Enhancing the therapeutic efficacy of dexamethasone for oral ulcers through adhesive gelatin hydrogel-based nano-delivery system

With excellent anti-inflammatory and immunomodulatory performances, dexamethasone (Dex) is widely used in the treatment of skin and mucosal ulcers. However, its therapeutic efficacy for oral ulcers is limited by the unique oral environment. To address this issue, we loaded dexamethasone into polylactic acid nanoparticles (PANs) and modified them with ligands to enhance their targeted delivery efficiency. These Dex-loaded PANs (Dex-PANs) were further incorporated into gelatin hydrogel to prolong the release of the drug with a single administration. A self-synthesized bisuccinimidyl-ester was used, for the first time, as the cross-linker to covalently adhere the gelatin hydrogel to the ulcer site, thereby resisting mechanical detachment or salivary erosion. Compared to the control group, the tensile strength of the cross-linked gelatin hydrogel adhesive on skin was increased by approximately 10-fold. Moreover, the gelatin hydrogel could maintain for over 5 days in saliva, during which it slowly degraded without detachment from the skin while releasing the Dex-loaded PANs. In vitro experiments demonstrated that the Dex-PANs incorporated in gelatin hydrogel exhibited no cytotoxicity and promoted the proliferation of gingival epithelial cells, accelerating ulcer healing. In vivo studies showed that the novel Dex formulation enabled rapid healing of oral ulcers with a single administration. This approach may contribute to advancements in medical adhesives and guide the creation of nanoparticle-based buccal delivery technologies.