ARTÍCULO

Hydrophobic gentamicin-loaded nanoparticles are effective against Brucella melitensis infection in mice

Autores: Imbuluzqueta Iturburua, Edurne; Gamazo de la Rasilla, Carlos Manuel; Lana Vega, Hugo; Campanero Martínez, Miguel Ángel; Salas Gómez, David; Gil Royo, Ana Gloria; Elizondo, E.; Ventosa , N.; Veciana , J.; Blanco Prieto, María José
Título de la revista: ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
ISSN: 0066-4804
Volumen: 57
Número: 7
Páginas: 3326 - 3333
Fecha de publicación: 2013
Resumen:
The clinical management of human brucellosis is still challenging and demands in vitro active antibiotics capable of targeting the pathogen-harboring intracellular compartments. A sustained release of the antibiotic at the site of infection would make it possible to reduce the number of required doses and thus the treatment-associated toxicity. In this study, a hydrophobically modified gentamicin, gentamicin-AOT [AOT is bis(2-ethylhexyl) sulfosuccinate sodium salt], was either microstructured or encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanoparticles. The efficacy of the formulations developed was studied both in vitro and in vivo. Gentamicin formulations reduced Brucella infection in experimentally infected THP-1 monocytes (>2-log10 unit reduction) when using clinically relevant concentrations (18 mg/liter). Moreover, in vivo studies demonstrated that gentamicin-AOT-loaded nanoparticles efficiently targeted the drug both to the liver and the spleen and maintained an antibiotic therapeutic concentration for up to 4 days in both organs. This resulted in an improved efficacy of the antibiotic in experimentally infected mice. Thus, while 14 doses of free gentamicin did not alter the course of the infection, only 4 doses of gentamicin-AOT-loaded nanoparticles reduced the splenic infection by 3.23 logs and eliminated it from 50% of the infected mice with no evidence of adverse toxic effects. These results strongly suggest that PLGA nanoparticles containing chemically modified hydrophobic gentamicin may be a promising alternative for the treatment of human brucellosis.