JAC Advance Access originally published online on April 21, 2004
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Journal of Antimicrobial Chemotherapy (2004) 53, 981-988
© 2004 The British Society for Antimicrobial Chemotherapy
Gentamicin-loaded microspheres for reducing the intracellular Brucella abortus load in infected monocytes
Departments of 1 Microbiology and 3 Pharmacy and Pharmaceutical Technology, University of Navarra, 31008 Pamplona, Spain; 2 Institute of Pharmaceutical Sciences, ETH, 8057 Zürich, Switzerland
Received 20 November 2003; returned 15 January 2004; revised and accepted 8 March 2004
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 µg of free or microencapsulated gentamicin and the efficacy of the treatments was measured after 24 h.
Results: The particle sizes were below 8 µm 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 log10) in comparison with untreated infected cells. Addition of 2% poloxamer 188 to the microsphere dispersion medium further reduced the infection (3.5 log10). 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 (
1 log10 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.
Keywords: biodegradable microspheres, drug delivery systems, Brucella-infected monocytes
* Present address. Division of Bacteriology, National Institute of Biological Standards and Control, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK.
Corresponding author. Tel: +34-948-425688; Fax: +34-948-425649; E-mail: cgamazo{at}unav.es
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