title: Multi-functional Liposomes Enhancing Target and Antibacterial Immunity for Antimicrobial and Anti-Biofilm Against Methicillin-Resistant Staphylococcus aureus.
abstract: OBJECTIVE
  The aim of this study was to prepare wheat germ agglutinin (WGA)-modified liposomes encapsulating clarithromycin and to evaluate their in vitro and in vivo efficacy against Methicillin-resistant Staphylococcus aureus (MRSA).
  
  
  METHODS
  Physicochemical parameters, minimum inhibitory concentrations, in vitro killing kinetic, cellular uptake, biofilm formation inhibition and pre-formed biofilm destruction, biodistribution, in vivo antibacterial efficacy against MRSA, and phagocytosis into macrophages for liposomes loading clarithromycin were determined.
  
  
  RESULTS
  The minimum inhibitory concentration and the time-kill curve for WGA-modified liposomal clarithromycin were better than those of free and nonmodified liposomal clarithromycin. Flow cytometry analysis displayed that liposomes could deliver more Coumarin 6, a fluorescent probe, into bacteria because of the conjugation of WGA. Besides, WGA-modified liposomal clarithromycin inhibited formation of S. aureus (ATCC 29213) and MRSA biofiom, and prompted the biofilm disassembly at lower concentrations below MIC. Effective accumulation of liposomes was displayed in the enterocoelia of the mice because of WGA. The number of MRSA colony-forming units in the kidney and spleen in mice treated with WGA-modified liposomal clarithromycin was significantly lower than that treated with free and nonmodified clarithromycin (p < 0.05). Intracellular localization of MRSA occurred in a significantly higher proportion of macrophage exposed to WGA-modified liposomes compared to those exposed to nonmodified liposomes.
  
  
  CONCLUSIONS
  Liposome modified by WGA is a promising formulation for bacteria targeted delivery and immunity defensive system through macrophage improving uptake of bacteria, biodistribution, in vitro and in vivo antibacterial efficacy against MRSA.
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.
authors.forename: Yansha
authors.initials: Y
authors.lastname: Meng
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, 100050, China.
authors.forename: Xucheng
authors.initials: X
authors.lastname: Hou
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.
authors.forename: Jiongxi
authors.initials: J
authors.lastname: Lei
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.
authors.forename: Shuangchen
authors.initials: S
authors.lastname: Cong
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, 100050, China.
authors.forename: Weiming
authors.initials: W
authors.lastname: Ding
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, 100050, China. liguiling99@gmail.com.
authors.forename: Guiling
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China. ll@bjmu.edu.cn.
authors.forename: Xinru
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000276:immunology* / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D017291:Clarithromycin / Q000276:immunology / Q000494:pharmacology; D007668:Kidney / Q000382:microbiology; D008081:Liposomes / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000276:immunology*; D051379:Mice; D008826:Microbial Sensitivity Tests / Q000379:methods; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D013154:Spleen / Q000382:microbiology; D014018:Tissue Distribution / Q000502:physiology; D014909:Wheat Germ Agglutinins / Q000276:immunology
chemical_list: D000900:Anti-Bacterial Agents; D008081:Liposomes; D014909:Wheat Germ Agglutinins; D017291:Clarithromycin
keywords: anti-biofilm; antimicrobial; immunity; multi-functional liposomes; targeting