Rubropunctatin-silver composite nanoliposomes for eradicating Helicobacter pylori in vitro and in vivo

Abstract

Helicobacter pylori (H. pylori) is a major factor in peptic ulcer disease and gastric cancer, and its infection rate is rising globally. The efficacy of traditional antibiotic treatment is less effective, mainly due to bacterial biofilms and the formation of antibiotic resistance. In addition, H. pylori colonizes the gastrointestinal epithelium covered by mucus layers, the drug must penetrate the double barrier of mucus layer and biofilm to reach the infection site and kill H. pylori. The ethanol injection method was used to synthesize nanoliposomes (EPI/R-AgNPs@RHL/PC) with a mixed lipid layer containing rhamnolipids (RHL) and phosphatidylcholine (PC) as a carrier, loaded with the urease inhibitor epiberberine (EPI) and the antimicrobial agent rubropunctatin silver nanoparticles (R-AgNPs). EPI/R-AgNPs@RHL/PC had the appropriate size, negative charge, and acid sensitivity to penetrate mucin-rich mucus layers and achieve acid-responsive drug release. In vitro experiments demonstrated that EPI/R-AgNPs@RHL/PC exhibited good antibacterial activity, effectively inhibited urease activity, removed the mature H. pylori biofilm, and inhibited biofilm regeneration. In vivo antibacterial tests showed that EPI/R-AgNPs@RHL/PC exhibited excellent activity in eradicating H. pylori and protecting the mucosa compared to the traditional clinical triple therapy, providing a new idea for the treatment of H. pylori infection.