Polyphenol-Modified Mg-Zn Layered Hydroxide-Contained Microneedle Patch Enhance Mucosal Repair by Remolding Diabetic Oral Microenvironment.

Diabetic oral ulcers pose a significant challenge in healing due to persistent inflammation. Despite local therapeutic interventions remaining the primary mode of treatment, the dynamic nature of the oral cavity, characterized by continuous muscular activity and salivary secretion, poses barriers to sustained drug retention and thereby limits therapeutic efficacy. To address this issue, an approach has been devised that aims to facilitate transdermal delivery of bioactive components to promote the healing of diabetic oral ulcers. A multifunctional soluble microneedle (MN) patch is prepared using γ-polyglutamic acid (γ-PGA), which is loaded with quercetin (Qu)-modified Mg-Zn layered hydroxide salt (LHS) nanosheets (LHSQ) with anti-inflammatory, antimicrobial and pro-angiogenic bioactivities to combat the diabetic oral ulcers. These findings demonstrate that the LHSQ-loaded MN (LHSQ-MN) patches are capable of effectively penetrating the oral mucosa. In a rat model of diabetic oral ulcers, the application of LHSQ-MN patches is found to facilitate the establishment of regeneration sites, regulate the inflammatory microenvironment of damaged tissues, exhibit potent antibacterial effects, expedite the reconstitution of the mucosal epithelium, and accelerate ulcer healing through the promotion of angiogenesis. These outcomes highlight the potential of LHSQ-MN patches as a promising therapeutic strategy for the management of oral ulcers in diabetic patients.