title: In vivo treatment of Helicobacter pylori infection with liposomal linolenic acid reduces colonization and ameliorates inflammation.
abstract: Helicobacter pylori infection is marked by a vast prevalence and strong association with various gastric diseases, including gastritis, peptic ulcers, and gastric cancer. Because of the rapid emergence of H. pylori strains resistant to existing antibiotics, current treatment regimens show a rapid decline of their eradication rates. Clearly, novel antibacterial strategies against H. pylori are urgently needed. Here, we investigated the in vivo therapeutic potential of liposomal linolenic acid (LipoLLA) for the treatment of H. pylori infection. The LipoLLA formulation with a size of ∼ 100 nm was prone to fusion with bacterial membrane, thereby directly releasing a high dose of linolenic acids into the bacterial membrane. LipoLLA penetrated the mucus layer of mouse stomach, and a significant portion of the administered LipoLLA was retained in the stomach lining up to 24 h after the oral administration. In vivo tests further confirmed that LipoLLA was able to kill H. pylori and reduce bacterial load in the mouse stomach. LipoLLA treatment was also shown to reduce the levels of proinflammatory cytokines including interleukin 1β, interleukin 6, and tumor necrosis factor alpha, which were otherwise elevated because of the H. pylori infection. Finally, a toxicity test demonstrated excellent biocompatibility of LipoLLA to normal mouse stomach. Collectively, results from this study indicate that LipoLLA is a promising, effective, and safe therapeutic agent for the treatment of H. pylori infection.
authors.affiliation: Department of NanoEngineering, Moores Cancer Center, and.
authors.forename: Soracha
authors.initials: S
authors.lastname: Thamphiwatana
authors.affiliation: Department of NanoEngineering, Moores Cancer Center, and.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Gao
authors.affiliation: Moores Cancer Center, and Department of Medicine, University of California, San Diego, La Jolla, CA 92093 zhang@ucsd.edu mobonyo@ucsd.edu.
authors.forename: Marygorret
authors.initials: M
authors.lastname: Obonyo
authors.affiliation: Department of NanoEngineering, Moores Cancer Center, and zhang@ucsd.edu mobonyo@ucsd.edu.
authors.forename: Liangfang
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents; D002277:Carcinoma / Q000188:drug therapy / Q000382:microbiology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects; D003362:Cost-Benefit Analysis; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial; D005230:Fatty Acids, Nonesterified / Q000737:chemistry; D005753:Gastric Mucosa / Q000378:metabolism; D016481:Helicobacter Infections / Q000188:drug therapy*; D016480:Helicobacter pylori / Q000187:drug effects*; D007249:Inflammation / Q000188:drug therapy*; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D050997:Nanomedicine; D013234:Stem Cells; D013270:Stomach / Q000382:microbiology; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000382:microbiology; D017962:alpha-Linolenic Acid / Q000008:administration & dosage*
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D005230:Fatty Acids, Nonesterified; D008081:Liposomes; D017962:alpha-Linolenic Acid
keywords: bacterial infection; drug delivery; free fatty acid; nanomedicine; nanotherapeutics