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Objectives: To evaluate the efficacy of gentamicin-loaded poly (lactide-co-glycolide) 50:50H (PLGA 50:50H) microspheres for the treatment of mice experimentally infected with Brucella abortus 2308.Methods: The microspheres were dispersed in either 2% (w/v) poloxamer 188 saline solution, or deionized water with the help of a cell homogenizer to break up particle aggregates, and were administered intravenously or intraperitoneally to B. abortus-infected mice 7 days post-infection.Results: Neither a single intravenous or intraperitoneal dose of 67 μg of gentamicin per mouse, nor three intraperitoneal doses of 100 μg of gentamicin per mouse, reduced the Brucella infection in the spleen compared with untreated mice 1 and 3 weeks post-treatment. Histological examination revealed granulation and tissue reaction in the periphery of spleen and liver of animals given three doses of the gentamicin-loaded microspheres.Conclusions: The lack of therapeutic activity of the gentamicin-loaded microspheres might be related to inappropriate microsphere size and aggregation, resulting also in a poor distribution of the microspheres in the spleen. The results might provide an example of practical problems related to particle size and aggregation for in vivo therapy with PLGA microspheres. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]