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 challenges 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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-09-01
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| Series: | Acta Pharmaceutica Sinica B |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383522002362 |
| _version_ | 1798031345923915776 |
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| author | Xiaonan Chen Yiqing Zou Shuqi Zhang Pengchao Fang Shuxuan Li Pengyu Li Yingying Sun Gang Yuan Haiyan Hu |
| author_facet | Xiaonan Chen Yiqing Zou Shuqi Zhang Pengchao Fang Shuxuan Li Pengyu Li Yingying Sun Gang Yuan Haiyan Hu |
| author_sort | Xiaonan Chen |
| collection | DOAJ |
| description | Helicobacter pylori (H. pylori), creating a global infection rate over 50%, presents great challenges 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 infection 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. Therefore, the study provides a “comprehensive attack” strategy for anti-H. pylori therapies including biofilms eradication tetralogy, immune activation and intracellular bacteria killing. |
| first_indexed | 2024-04-11T19:56:03Z |
| format | Article |
| id | doaj.art-92a3e0c14f6346fc9e2e3e6d969c78f4 |
| institution | Directory Open Access Journal |
| issn | 2211-3835 |
| language | English |
| last_indexed | 2024-04-11T19:56:03Z |
| publishDate | 2022-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-92a3e0c14f6346fc9e2e3e6d969c78f42022-12-22T04:06:03ZengElsevierActa Pharmaceutica Sinica B2211-38352022-09-0112934983512Multi-functional vesicles improve Helicobacter pylori eradication by a comprehensive strategy based on complex pathological microenvironmentXiaonan Chen0Yiqing Zou1Shuqi Zhang2Pengchao Fang3Shuxuan Li4Pengyu Li5Yingying Sun6Gang Yuan7Haiyan Hu8Lab of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaLab of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaLab of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaLab of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaLab of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaLab of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaLab of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaPhase I Clinical Trial Center, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China; Department of Geriatrics, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, ChinaLab of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China; Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, Sun Yat-sen University, Guangzhou 510006, China; Corresponding author.Helicobacter pylori (H. pylori), creating a global infection rate over 50%, presents great challenges 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 infection 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. Therefore, the study provides a “comprehensive attack” strategy for anti-H. pylori therapies including biofilms eradication tetralogy, immune activation and intracellular bacteria killing.http://www.sciencedirect.com/science/article/pii/S2211383522002362Helicobacter pyloriPharmaceutical preparationsBiofilmsBiofilms eradication tetralogyImmune evasionLipid raft |
| spellingShingle | Xiaonan Chen Yiqing Zou Shuqi Zhang Pengchao Fang Shuxuan Li Pengyu Li Yingying Sun Gang Yuan Haiyan Hu Multi-functional vesicles improve Helicobacter pylori eradication by a comprehensive strategy based on complex pathological microenvironment Acta Pharmaceutica Sinica B Helicobacter pylori Pharmaceutical preparations Biofilms Biofilms eradication tetralogy Immune evasion Lipid raft |
| title | Multi-functional vesicles improve Helicobacter pylori eradication by a comprehensive strategy based on complex pathological microenvironment |
| title_full | Multi-functional vesicles improve Helicobacter pylori eradication by a comprehensive strategy based on complex pathological microenvironment |
| title_fullStr | Multi-functional vesicles improve Helicobacter pylori eradication by a comprehensive strategy based on complex pathological microenvironment |
| title_full_unstemmed | Multi-functional vesicles improve Helicobacter pylori eradication by a comprehensive strategy based on complex pathological microenvironment |
| title_short | Multi-functional vesicles improve Helicobacter pylori eradication by a comprehensive strategy based on complex pathological microenvironment |
| title_sort | multi functional vesicles improve helicobacter pylori eradication by a comprehensive strategy based on complex pathological microenvironment |
| topic | Helicobacter pylori Pharmaceutical preparations Biofilms Biofilms eradication tetralogy Immune evasion Lipid raft |
| url | http://www.sciencedirect.com/science/article/pii/S2211383522002362 |
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