Microneedle Patch Loaded with Metabolized Elastin-Complexed Ceria Nanoparticles for Oral Ulcer Treatment

Abstract

Oral ulcers are prevalent oral health issues with a high recurrence rate that substantially impair oral and systemic health. However, current therapies for oral ulcers are limited to symptom relief without addressing its fundamental pathophysiology. Additionally, their treatment efficacy is limited by reduced bioavailability due to the dynamic environment of oral cavity and reactive oxygen species (ROS)-rich microenvironment of ulcer bed. Here, we develop a microneedle patch system designed to locally deliver metabolized elastin-complexed ceria nanoparticles (mEl-Ce) and triamcinolone acetonide (TA) for combination treatment of oral ulcers. Elastin, an elastic protein fiber and a major component of the extracellular matrix, is metabolized to facilitate the formation of ceria nanoparticles and becomes integrated with them as a complex, termed mEl-Ce. The synthetic corticosteroid TA is codelivered with mEl-Ce, loaded into poly(vinyl alcohol)- and poly(vinylpyrrolidone)-based dissolvable microneedle tips. The system is designed so that mEl-Ce in the tip layer is released rapidly upon application to scavenge excess ROS and create a favorable microenvironment for drug action, while TA in the base layer is released in a sustained manner to provide prolonged anti-inflammatory effects. mEl-Ce demonstrates enhanced efficacy in neutralizing ROS and promoting angiogenesis to support ulcer healing, whereas TA topically alleviates ulcer symptoms. An additional adhesive hydrogel layer was integrated into the microneedle patch to ensure firm attachment at the lesion site and to serve as a protective barrier against salivary enzymes and microbial infiltration. This design enables controlled, sustained release of therapeutic agents and effectively treats a recurrent aphthous ulcer in a mouse model. Our system provides an optimized topical delivery strategy for therapeutic agents to address oral diseases efficiently.