Chitosan-sodium tripolyphosphate-zinc nanogel for synergistic hydrogen and ion release to eradicate Helicobacter pylori and promote gastric mucosal healing

This study developed a chitosan (CS)‑sodium tripolyphosphate (TPP)‑zinc (Zn) nanogel for treating Helicobacter pylori ( H. pylori ) through synergistic antibacterial, anti-inflammatory, and mucosal repair mechanisms. The nanogel was synthesized via an emulsion method, leveraging electrostatic interactions between CS amino groups and TPP phosphate ions, followed by Zn incorporation. Characterization revealed uniform spherical nanoparticles (~200 nm) with high Zn content (20.18 %) and controlled hydrogen (H 2 ) and Zn 2+ release (15 h) in acidic environments. In vitro assays demonstrated potent antibacterial activity against H. pylori (95.83 % inhibition at pH = 2; 28.54 % inhibition at pH = 7) attributed to Zn 2+ -mediated enzyme disruption. The nanogel exhibited significant antioxidant capacity, scavenging 82.3 % of PTIO and 65.48 % of DPPH radicals. Biocompatibility testing confirmed minimal haemolysis (<5 %) and high cell viability (>95 %). In vivo studies in H. pylori -infected mice demonstrated a bacterial inhibition rate of 97.54 % through upregulation of β-catenin and tight junction proteins. Concurrently, mucosal repair was enhanced, achieving migration rates of 44.2 ± 5.6 % and 72.34 ± 2.1 % at 12 and 24 h respectively. The nanogel also preserved gut microbiota diversity post-treatment, unlike conventional antibiotics. This multifunctional nanogel platform combines biocompatibility, ease of manufacture and dual therapeutic effects. In summary, this study proposes a multifunctional therapeutic strategy capable of simultaneously addressing H. pylori infection, gastric inflammation and mucosal damage. It offers a paradigm shift from traditional antibiotic-centred therapies, providing a promising strategy for eradicating Helicobacter pylori and restoring gastric injury.