An all-in-one therapeutic platform for the treatment of resistant Helicobacter pylori infection

Abstract

Helicobacter pylori (H. pylori) infection is a major cause of gastric diseases. Currently, bismuth-based quadruple therapy is widely adopted for eradicating H. pylori infection. However, this first-line strategy faces several challenges such as drug resistance, intestinal dysbacteriosis, and patients’ poor compliance. To overcome these problems, an all-in-one therapeutic platform (CLA-Bi-ZnO2@Lipo) that composed of liposomes loading clarithromycin (CLA), Bi, and ZnO2 hybrid nanoparticles was developed for eradicating multidrug-resistant (MDR) H. pylori. The in vitro and in vivo results showed that CLA-Bi-ZnO2@Lipo could target the infection-induced inflammatory mucosa through liposome mediated nanoparticle-tissue surface charge interaction and quickly respond to the gastric acid environment to release CLA, Bi3+, Zn2+, and H2O2. By oral administration per day, the acid triggered decomposition of CLA-Bi-ZnO2@Lipo could significantly increase intragastric pH to 6 within 30 min; The released CLA, Zn2+, and H2O2 further exerted synergistical anti-bacterial effects in which a ∼2 order higher efficacy in reducing MDR H. pylori burden was achieved in comparison with standard quadruple therapy (p < 0.05); The released Zn2+ and Bi3+ could also alleviate mucosal inflammation. Most importantly, the CLA-Bi-ZnO2@Lipo exhibited superior biosafety and nearly no side effects on intestinal flora. Overall, this study developed a highly integrated and safe anti-MDR H. pylori agent which had great potential to be used as an alternative treatment for MDR H. pylori eradication.