Breaking drug dependency: a self-antioxidant bilayer patch for oral ulcer treatment.

Oral ulcers (OUs) are a common ailment of the oral mucosa, leading to pain or even systemic illness affecting patient's daily lives. Current oral patch strategies primarily address the wet and dynamic environment of the oral cavity, but often overlook the immune-inflammatory responses with elevated oxidative stress, where reactive oxygen species (ROS) exacerbate tissue damage and delay healing. Moreover, drug-related cytotoxicity limits their clinical utility, necessitating drug-free therapeutic alternatives. Herein, a drug-free, asymmetric adhesion patch with ROS-scavenging capability was developed for OU treatment. The adhesion layer comprises poly-glycine conjugated to β-cyclodextrin (β-CD) via a diselenide bond, enabling localized ROS-scavenging, selenium supply and potential responsive drug release. The lubricating layer was formed by self-assembly of fluorenylmethyloxycarbonyl-diphenylalanine (Fmoc-FF) on the acidic adhesion surface. In rat OU models, the asymmetric patch exhibited instant wet adhesion and effective anti-inflammation. The Se-donor regulates the cellular redox status by promoting GPx-4 biosynthesis, thereby maintaining redox homeostasis and accelerating OU healing.