Yansha Meng1, Xucheng Hou2, Jiongxi Lei1, Mengmeng Chen1, Shuangchen Cong1, Yuanyuan Zhang1, Weiming Ding2, Guiling Li3, Xinru Li4. 1. Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China. 2. Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, 100050, China. 3. Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, 100050, China. liguiling99@gmail.com. 4. Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China. ll@bjmu.edu.cn.
Abstract
PURPOSE: 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.
PURPOSE: 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: H Valizadeh; G Mohammadi; R Ehyaei; M Milani; M Azhdarzadeh; P Zakeri-Milani; F Lotfipour Journal: Pharmazie Date: 2012-01 Impact factor: 1.267
Authors: Pan-Pan Wu; Hao He; W David Hong; Tong-Rong Wu; Gui-Ying Huang; Ying-Ying Zhong; Bo-Rong Tu; Min Gao; Jun Zhou; Su-Qing Zhao; Dong-Li Li; Xue-Tao Xu; Zhao-Jun Sheng; Stephen A Ward; Paul M O'Neill; Kun Zhang Journal: Infect Drug Resist Date: 2018-10-24 Impact factor: 4.003