JAC Advance Access originally published online on June 23, 2006
Journal of Antimicrobial Chemotherapy 2006 58(3):549-556; doi:10.1093/jac/dkl257
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Intracellular killing of Brucella melitensis in human macrophages with microsphere-encapsulated gentamicin
1 Department of Microbiology, University of Navarra Irunlarrea 1, 31080 Pamplona, Spain 2 Department of Pharmacy and Pharmaceutical Technology, University of Navarra Irunlarrea 1, 31080 Pamplona, Spain 3 Department of Histology and Pathology, University of Navarra Irunlarrea 1, 31080 Pamplona, Spain
Received 17 March 2006; returned 3 May 2006; revised 8 May 2006; accepted 30 May 2006
*Corresponding author. Tel: +34-948425600; Fax: +34-948425649; E-mail: cgamazo{at}unav.es
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 µg 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.
Keywords: microparticles , brucellosis , phagocytosis , drug delivery system
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