Polydopamine-mediated multi-stage delivery for precise local therapy of Helicobacter pylori-infected gastric ulcers

The effective treatment of Helicobacter pylori-infected gastric ulcers requires precise local delivery of antibiotics to the deep-seated pathogens within the inflamed tissue. However, the complex gastric environment poses significant biological barriers, necessitating distinct functional requirements for efficient mucus penetration and robust bacterial adhesion. In this study, we developed polydopamine-functionalized and clarithromycin-loaded nanoparticles designed for a sequential multi-stage delivery cascade. The polydopamine-mediated interface provided colloidal stability in the acidic gastric lumen, reduced premature drug leakage, and facilitated mucus penetration by minimizing interactions with the mucin network. At the infection site, the chemical properties of the functionalized surface facilitated robust and ligand-independent adhesion to Helicobacter pylori. In vivo investigations using a murine model revealed nanoparticle penetration of up to 400 μm into the ulcerated tissue. This precise targeting yielded approximately 99.9% bacterial reduction, significantly accelerating ulcer healing at an antibiotic dose 10-fold lower than that used in conventional systemic therapy. These findings establish the polydopamine-mediated delivery cascade as a promising platform for the precise local treatment of Helicobacter pylori-associated inflammatory gastric diseases.