Multi-functional vesicles improve Helicobacter pylori eradication by a comprehensive strategy based on complex pathological microenvironment

Helicobacter pylori (H. pylori), creating a global infection rate over 50%, presents great chal-lenges in clinical therapies due to its complex pathological microenvironment in vivo. To improve the eradication efficacy, herein we fabricated a pharmaceutical vesicle RHL/Cl-Ch-cal where cholesterol -PEG, calcitriol and first-line antibiotic clarithromycin were co-loaded in the rhamnolipid-composed outer lipid layer. RHL/Cl-Ch-cal could quickly penetrate through gastric mucus layer to reach H. pylori infec-tion sites, and then effectively destroyed the architecture of H. pylori biofilms, killed dispersed H. pylori and inhibited the re-adhesion of residual bacteria (called biofilms eradication tetralogy). Moreover, RHL/ Cl-Ch-cal activated the host immune response to H. pylori by replenishing cholesterol to repair lipid raft on the cell membrane of host epithelial cells. Finally, RHL/Cl-Ch-cal killed the intracellular H. pylori through recovering the lysosomal acidification and assisting degradation. In experiments, RHL/Cl-Ch-cal demonstrated prominent anti -H. pylori efficacy in the classical H. pylori-infected mice model. There-fore, the study provides a comprehensive attack strategy for anti -H. pylori therapies including biofilms eradication tetralogy, immune activation and intracellular bacteria killing. 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

This study developed a pharmaceutical vesicle RHL/Cl-Ch-cal that showed promising effects in combating Helicobacter pylori (H. pylori) infection. Through a combination of cholesterol-PEG, calcitriol, and clarithromycin, RHL/Cl-Ch-cal effectively disrupted the architecture of H. pylori biofilms, killed dispersed bacteria, and inhibited bacterial re-adhesion. Moreover, it activated the host immune response and killed intracellular H. pylori. The study provides a comprehensive attack strategy for H. pylori therapies.