A poly(lipoic acid)-based binary elastomeric patch for treating oral leukoplakia

Oral leukoplakia (OLK) is a prevalent oral potentially malignant disorder. Targeting the core pathogenesis of OLK, we herein develop a poly(lipoic acid)-based bioadhesive elastomeric patch via a one-step solvent evaporation strategy by integrating lipoic acid with lauroyl arginate ethyl ester hydrochloride, an FDA-approved antimicrobial agent. In this binary system, LAE self-assembles into nanomicelles with outwardly radiating guanidino groups acting as "multi-armed grippers" that suppress room-temperature depolymerization of PolyLA through multiple hydrogen bonds and electrostatic interactions with carboxyl groups. The abundant carboxyl groups on the elastomer surface provide excellent wet tissue adhesion suitable for the dynamic oral environment. Surfactants with distinct terminal groups are further applied to validate the universality of this binary design strategy and to clarify the regulatory effects of intermolecular interaction strength on material stability, crystallinity and mechanical performance. In vitro biological evaluations demonstrate that the PolyLA/LAE patch can efficiently scavenge ROS, inhibit C. albicans proliferation, and induce apoptosis of dysplastic oral keratinocytes, while maintaining favorable biocompatibility. In a rat OLK model, the patch exhibits satisfactory therapeutic outcomes that are comparable to clinical vitamin A ointment. Collectively, this binary synergistic elastomeric patch offers a simple and universal strategy for treating refractory oral mucosal lesions represented by oral leukoplakia.