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

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 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: Concepción Lecároz, María J Blanco-Prieto, María A Burrell, Carlos Gamazo
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 58 Issue 3 Pg. 549-56 (Sep 2006) ISSN: 0305-7453 [Print] England
• PMID: 16799160 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Drug Carriers
• Gentamicins
• Polymers
• Polylactic Acid-Polyglycolic Acid Copolymer
• Polyglycolic Acid
• Lactic Acid

Topics

• Anti-Bacterial Agents (administration & dosage, chemistry, pharmacology)
• Brucella melitensis (drug effects)
• Cell Line
• Drug Carriers (chemistry)
• Gentamicins (administration & dosage, chemistry, pharmacology)
• Humans
• Lactic Acid (chemistry)
• Macrophages (microbiology)
• Microspheres
• Nanostructures (chemistry)
• Particle Size
• Phagocytosis (drug effects)
• Polyglycolic Acid (chemistry)
• Polylactic Acid-Polyglycolic Acid Copolymer
• Polymers (chemistry)
• Respiratory Burst (drug effects)
• Solubility