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JAC Advance Access published online on June 23, 2006
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkl257
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
Received March 17, 2006
Revised May 8, 2006
Accepted May 30, 2006

Original article

Intracellular killing of Brucella melitensis in human macrophages with microsphere-encapsulated gentamicin

Concepción Lecároz 1, María J. Blanco-Prieto 2, María A. Burrell 3, and Carlos Gamazo 1 *

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

* To whom correspondence should be addressed.
Carlos Gamazo, E-mail: cgamazo{at}unav.es


  Abstract

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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