OBJECTIVES: Treatment of human brucellosis demands antibiotic targeting into the mononuclear-phagocytic system. The aim of this work was to prepare and characterize particulate carriers containing gentamicin and to study their interactions with phagocytic cells and bactericidal activity against intracellular Brucella melitensis. METHODS: Different poly(lactide-co-glycolide) (PLGA) polymers with free carboxylic end-group were used to formulate micro- and nanoparticles containing gentamicin, by a water-oil-water solvent-evaporation technique. PLGA 502H and 75:25H microparticles were selected because they showed the highest gentamicin loadings as well as good physico-chemical properties and sustained release in vitro. RESULTS: Gentamicin-containing microspheres of both polymers were successfully phagocytosed by infected THP-1 human monocytes, and immunocytochemistry studies revealed that the antibiotic reached Brucella-specific compartments. A dose of 30 microg of encapsulated gentamicin was able to reduce intracellular Brucella infection by 2.2 log. CONCLUSIONS: Altogether, these results suggest that 502H and 75:25H microspheres are suitable carriers for gentamicin targeting inside human macrophages and thus for brucellosis treatment.
OBJECTIVES: Treatment of humanbrucellosis demands antibiotic targeting into the mononuclear-phagocytic system. The aim of this work was to prepare and characterize particulate carriers containing gentamicin and to study their interactions with phagocytic cells and bactericidal activity against intracellular Brucella melitensis. METHODS: Different poly(lactide-co-glycolide) (PLGA) polymers with free carboxylic end-group were used to formulate micro- and nanoparticles containing gentamicin, by a water-oil-water solvent-evaporation technique. PLGA 502H and 75:25H microparticles were selected because they showed the highest gentamicin loadings as well as good physico-chemical properties and sustained release in vitro. RESULTS:Gentamicin-containing microspheres of both polymers were successfully phagocytosed by infected THP-1human monocytes, and immunocytochemistry studies revealed that the antibiotic reached Brucella-specific compartments. A dose of 30 microg of encapsulated gentamicin was able to reduce intracellular Brucella infection by 2.2 log. CONCLUSIONS: Altogether, these results suggest that 502H and 75:25H microspheres are suitable carriers for gentamicin targeting inside human macrophages and thus for brucellosis treatment.
Authors: Laetitia G Garcia; Sandrine Lemaire; Barbara C Kahl; Karsten Becker; Richard A Proctor; Paul M Tulkens; Françoise Van Bambeke Journal: Antimicrob Agents Chemother Date: 2012-09-17 Impact factor: 5.191
Authors: L G Garcia; S Lemaire; B C Kahl; K Becker; R A Proctor; O Denis; P M Tulkens; F Van Bambeke Journal: Antimicrob Agents Chemother Date: 2012-05-07 Impact factor: 5.191
Authors: Sharif M Abdelghany; Derek J Quinn; Rebecca J Ingram; Brendan F Gilmore; Ryan F Donnelly; Clifford C Taggart; Christopher J Scott Journal: Int J Nanomedicine Date: 2012-07-26
Authors: Javier Ariza; Mile Bosilkovski; Antonio Cascio; Juan D Colmenero; Michael J Corbel; Matthew E Falagas; Ziad A Memish; Mohammad Reza Hasanjani Roushan; Ethan Rubinstein; Nikolaos V Sipsas; Javier Solera; Edward J Young; Georgios Pappas Journal: PLoS Med Date: 2007-12 Impact factor: 11.069