A poly(γ-glutamic acid)-based Mucoadhesive hydrogel incorporating arginine for preventing acute alcohol-induced gastric injury

An arginine-functionalized poly(γ-glutamic acid)-based hydrogel was constructed via dynamic disulfide cross-linking. • The hydrogel displayed enhanced mucoadhesion and prolonged gastric retention in mice. • Arginine incorporation enabled NO-related antioxidant and anti-inflammatory effects. • The hydrogel significantly protected against alcohol-induced gastric injury with favorable biosafety. Alcohol-induced gastric injury caused by excessive alcohol consumption is characterized by oxidative stress and inflammatory cascades that form a vicious cycle, leading to progressive gastric mucosal damage. Existing interventions, which are limited in their functional scope, are unable to effectively address this complex condition, underscoring the urgent need to develop safe and effective protective strategies. Here, a novel disulfide-crosslinked hydrogel was constructed using poly(γ-glutamic acid) (γ-PGA) and lipoic acid (LA), with arginine (Arg) incorporated via hydrogen bonding to obtain Arg-gel, as characterized by NMR and FT-IR. The 8% ( w / v ) gel exhibits excellent mucosal adhesion and extends the retention time in the stomach from 15 to 30 min to 2–4 h. In vitro, Arg-gel demonstrated dose-dependent antioxidant activity and significantly reduced intracellular ROS in alcohol-stimulated GES-1 cells, while also suppressing pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and restoring mitochondrial function. In a mouse model of acute alcohol-induced gastric injury, Arg-gel markedly reduced the ulcer index and facilitated the restoration of mucosal architecture and PGE2 levels. No significant toxicity was observed in a 14-day biosafety assessment. Collectively, Arg-gel exhibits promising gastroprotective effects and biosafety, offering a novel strategy for gastric mucosal protection. Synthesis of the Arg-gel hydrogel and its evaluation in alleviating alcohol-induced gastric injury in mice. (a)The primary synthetic raw materials and structural formulae of hydrogels based on polyglutamic acid. (b) Cross-linking mechanism driven primarily by disulfide bond formation. (c) In vivo evaluation using an acute alcohol-induced gastric injury model. Download: Download high-res image (188KB) Download: Download full-size image