JAC Advance Access originally published online on May 9, 2005
Journal of Antimicrobial Chemotherapy 2005 55(6):1032-1036; doi:10.1093/jac/dki144
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Gentamicin-loaded microspheres for treatment of experimental Brucella abortus infection in mice
1 Department of Microbiology, University of Navarra, 31008 Pamplona, Navarra, Spain; 2 Institute of Pharmaceutical Sciences, ETH, 8057 Zurich, Switzerland; 3 Department of Pharmacy and Pharmaceutical Technology, University of Navarra, 31008 Pamplona, Navarra, Spain
* Corresponding author. Tel: +34-948-425688; Fax: +34-948-425649; Email: cgamazo{at}unav.es
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.
Keywords: biodegradable microspheres , drug delivery systems , Brucella-infected mice
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