A mucoadhesive nanotherapeutic platform orchestrating acid control and redox homeostasis for enhanced gastric ulcer healing.

Conventional oral therapies for gastric ulcers are often limited by rapid gastric clearance and insufficient local drug accumulation, resulting in suboptimal therapeutic outcomes. Here, we developed a dopamine-modified poly(β-amino ester) (DA-PBAE) mucoadhesive nanoplatform for the oral co-delivery of vonoprazan and edaravone (VE@DA-PBAE). The amphiphilic DA-PBAE nanoparticles were constructed through a one-pot Michael addition reaction and integrated acid-triggered electrostatic interactions with catechol-mediated wet adhesion, enabling prolonged gastric mucosal retention and sustained release of dual therapeutic agents in the highly acidic gastric environment. VE@DA-PBAE exhibited excellent colloidal stability, favorable drug-loading properties, and outstanding biocompatibility in vitro. In an acetic acid-induced gastric ulcer rat model, VE@DA-PBAE markedly accelerated ulcer healing by alleviating oxidative stress and inflammatory responses, enhancing superoxide dismutase activity, reducing malondialdehyde accumulation, and promoting epithelial regeneration and collagen remodeling. Notably, VE@DA-PBAE achieved superior therapeutic efficacy compared with free drugs and clinically used sucralfate, without requiring additional combination therapies. This multifunctional mucoadhesive nanoplatform provides an effective oral strategy integrating acid suppression and antioxidative repair for enhanced gastric ulcer therapy.