title: Preparation and evaluation of lipid polymer nanoparticles for eradicating H. pylori biofilm and impairing antibacterial resistance in vitro.
abstract: The resistance of Helicobacter pylori to classical antimicrobial treatment has become increasingly common, whereupon biofilms are considered to play an important role in the resistance mechanism. Here 10.2% of amoxicillin (AMX) and a novel anti H. pylori adhesion material pectin sulfate (PECS) loaded lipid polymer nanoparticles (LPN) were prepared, with rhamnolipid and phospholipids as the outer mixed lipids layer (RHL-PC-LPN). The size of RHL-PC-LPN was around 200 nm, was negatively-charged, and showed sustained and complete drug release within 24h. In an in vitro study, H. pylori biofilm models were successfully established. RHL-PC-LPN, superior to PC-LPN (employing phospholipids only as the outer lipid layer), PECS+AMX (mixture of PECS and AMX) and AMX only, was proven to significantly eradicate H. pylori in the biofilm form. In accordance to our previous results, the RHL-PC-LPN group, together with the PC-LPN and PECS+AMX group, inhibited H. pylori from adhering to AGS cells. Investigating the underlying mechanisms contributing to the death of H. pylori caused by RHL-PC-LPN, we found that LPN could lower the antibiotic minimal inhibition concentration (MIC) to biofilm form from 125 μg/ml to 15.6 μg/ml. Furthermore, FITC-ConA labeled extracellular polymeric substances (EPS) were decreased in the RHL-PC-LPN group observed by a laser scanning confocal microscope. Therefore, we conclude that employing the mixed lipids of rhamnolipid and phospholipids as the outer layer of nanoparticles and PECS as the inner core produces a system capable of significantly disrupting H. pylori biofilm by eliminating the EPS as well as inhibiting the adherence and colonization of bacteria.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou 510006, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Cai
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou 510006, PR China.
authors.forename: Huizhi
authors.initials: H
authors.lastname: Huang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou 510006, PR China.
authors.forename: Weijuan
authors.initials: W
authors.lastname: Song
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou 510006, PR China. Electronic address: lsshhy@mail.sysu.edu.cn.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan II Road, Guangzhou 510080, PR China.
authors.forename: Jiesi
authors.initials: J
authors.lastname: Chen
authors.affiliation: Guangdong General Hospital, Guangzhou 510080, PR China.
authors.forename: Liyan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou 510006, PR China.
authors.forename: Pengyu
authors.initials: P
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou 510006, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wu
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou 510006, PR China.
authors.forename: Chuanbin
authors.initials: C
authors.lastname: Wu
mesh_terms: D000658:Amoxicillin / Q000008:administration & dosage* / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D065546:Drug Liberation; D024881:Drug Resistance, Bacterial; D006017:Glycolipids / Q000737:chemistry; D016480:Helicobacter pylori / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D053758:Nanoparticles; D010368:Pectins / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry; D011108:Polymers / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D003692:Delayed-Action Preparations; D006017:Glycolipids; D010743:Phospholipids; D011108:Polymers; C418382:rhamnolipid; D000658:Amoxicillin; D010368:Pectins
keywords: Extracellular polymeric substance; H. pylori biofilm; Lipid polymer nanoparticles; Pectin sulfate; Rhamnolipid