Brucellosis is a worldwide zoonosis caused by different species of the genus Brucella. The intracellular localisation of this pathogen, particularly in macrophages, renders treatment difficult since most
antibiotics known to be efficient in vitro do not actively pass through cellular membranes. As alternative to current treatment, polymeric drug delivery systems containing
gentamicin have been developed. These particulate carriers target the
drug into the mononuclear-phagocytic system, where the pathogen resides that will allow intracellular accumulation of the
antibiotic after particle degradation. Besides, particle uptake may induce macrophage activation, increasing the production of
reactive oxygen intermediates, involved in host defense against the intracellular pathogen. The aim of the present work was to study the suitability of polymeric nanoparticles for
gentamicin entrapment in view to treat
brucellosis. Different
poly(lactide-co-glycolide) PLGA
polymers were used to formulate the nanoparticles containing
gentamicin by a water-oil-water
solvent evaporation method. Furthermore, in vitro macrophage activation upon nanoparticles phagocytosis and in vivo distribution of the nanocarriers in the target organs for Brucella (liver and spleen) were also studied. The nanoparticle sizes were below 350 nm, the
gentamicin encapsulation efficiency depended on the
polymer type used for their preparation and the in vitro release of the
antibiotic exhibited a continuos pattern (PLGA 502H). PLGA 502H nanoparticles were the most suitable due to the highest entrapment and the most sustained release. The nanoparticles were successfully phagocyted by a J774 murine monocytes cell line and biodistribution studies in mice after
intravenous administration of the delivery systems revealed that the particles reached the target organs of Brucella (liver and spleen). All together, these results indicate that the nanocarriers described in this work may be suitable as
gentamicin delivery system to control
brucellosis.