Gentamicin-loaded microspheres for reducing the intracellular Brucella abortus load in infected monocytes.

Abstract

OBJECTIVES:

The intracellular antibiotic efficiency of gentamicin-loaded microspheres in the context of Brucella-infected murine monocytes was examined in vitro with a view to developing improved therapies for the treatment of brucellosis.

METHODS:

Biodegradable microspheres made of end-group capped and uncapped poly(lactide-co-glycolide) 50:50 (PLGA 50:50 and PLGA 50:50H) and containing gentamicin sulphate were used to target Brucella abortus-infected J774 monocyte-macrophages. The infected cells were treated with 15 micro g of free or microencapsulated gentamicin and the efficacy of the treatments was measured after 24 h.

RESULTS:

The particle sizes were below 8 micro m and in vitro release of gentamicin from the microspheres followed a continuous (PLGA 50:50H) or a multiphasic (PLGA 50:50) pattern over 50 days. Treatment with gentamicin microencapsulated into the end-group uncapped PLGA 50:50H microspheres, decreased significantly the number of intracellular bacteria (typically by 2 log(10)) in comparison with untreated infected cells. Addition of 2% poloxamer 188 to the microsphere dispersion medium further reduced the infection (3.5 log(10)). Opsonization of the particles with non-immune mouse serum had no effect on the antibacterial efficacy of the microspheres. End-group capped PLGA 50:50 type microspheres containing the antibiotic were less effective at reducing intracellular bacteria ( approximately 1 log(10) reduction), although addition of poloxamer 188 to the dispersion medium again enhanced their intracellular antibacterial activity. Placebo PLGA 50:50 and PLGA 50:50H microspheres had no bactericidal activity.

CONCLUSIONS:

The results indicate that PLGA 50:50-microencapsulated gentamicin sulphate may be suitable for efficient drug targeting and delivery to reduce intracellular Brucella infections.

• Authors: Sandra Prior, Bruno Gander, Concepción Lecároz, Juan M Irache, Carlos Gamazo
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 53 Issue 6 Pg. 981-8 (Jun 2004) ISSN: 0305-7453 [Print] England
• PMID: 15102748 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Animals
• Anti-Bacterial Agents (administration & dosage, pharmacology)
• Brucella abortus (drug effects)
• Brucellosis (microbiology)
• Cell Line
• Drug Compounding
• Gentamicins (administration & dosage, pharmacology)
• Lactic Acid
• Mice
• Microspheres
• Monocytes (drug effects, microbiology)
• Particle Size
• Phagocytosis
• Polyglycolic Acid
• Polylactic Acid-Polyglycolic Acid Copolymer
• Polymers
• Respiratory Burst (drug effects)