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|Gentamicin-loaded microspheres for reducing the intracellular Brucella abortus load in infected monocytes|
|Authors: ||Prior, S. (Sandra)|
Gander, B. (Bruno)
Lecaroz, M.C. (María Concepción)
Irache, J.M. (Juan Manuel)
Gamazo, C. (Carlos)
|Keywords: ||Biodegradable microspheres|
Drug delivery systems
|Issue Date: ||2004|
|Publisher: ||Oxford University Press|
|Publisher version: ||http://dx.doi.org/10.1093/jac/dkh227|
|Citation: ||Prior S, Gander B, Lecaroz C, Irache JM, Gamazo C. Gentamicin-loaded microspheres for reducing the intracellular brucella abortus load in infected monocytes. J Antimicrob Chemother. 2004 Jun;53(6):981-8.|
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.
|Permanent link: ||http://hdl.handle.net/10171/19188|
|Appears in Collections:||DA - Farmacia - Tecnología Farmacéutica - Artículos de revista|
DA - Medicina - Microbiología y Parasitología - Artículos de revista
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