Tratamiento de la brucelosisefecto de la gentamicina encapsulada en micro y manopartículas de plga

Supervised by:
  1. Carlos Gamazo Director
  2. María José Blanco Prieto Co-director

Defence university: Universidad de Navarra

Fecha de defensa: 16 December 2005

  1. Ramón Luis Diáz García Chair
  2. Miguel Angel Campanero Martinez Secretary
  3. Carmen María Evora García Committee member
  4. Javier Ariza Cardenal Committee member
  5. Antonio Orduña Domingo Committee member

Type: Thesis

Teseo: 300113 DIALNET


TITULO: TRATAMIENTO DE LA BRUCELOSIS: EFECTO DE LA GENTAMICINA ENCAPSULADA EN MICRO Y NANOPARTICULAS DE PLGA #RESUMEN: BRUCELLOSIS TREATMENT: EFFECT OF GENTAMICIN LOADED INTO MICRO AND NANOPARTICLES OF PLGA Human brucellosis is a worldwide zoonosis caused by Brucella: facultative intracellular pathogen of phagocytes. Regarding antibiotic treatment relapses remain a problem. Aminoglycosides are bactericidal antibiotics showing high in vitro activity against the pathogen, but due to their polar nature, access to intracellular environment is restricted. As alternative to current therapy, the present work evaluates gentamicin targeting using drug delivery systems of biodegradable co-polymers of lactic and glycolic acids (PLGA) prepared by "solvent evaporation" method. Selected formulations (microparticles made of PLGA 75:25H and micro and nanoparticles of 502h) presented suitable physico-chemical properties and drug "loading, able to activate monocytes (useful for intracellular elimination of the pathogen). in vivo studies showed their uptake by macrophages of liver and spleen (main target organs for the pathogen). Since a sustained release is desired, nanoparticles were discarded due to their fast degradation. Microspheres made of PLGA 502H were degraded within the first two weeks, while 75:25H microspheres evidenced a more sustained release. Experimental macrophagic infection with B. melitensis and further treatment with both formulations showed similar intracellular reduction, significantly different from free antibiotic. Pharmacokinetics reflected the controllea release of gentamicin, and its accumulation inside pathogen's target organs. In liver, no differences were observed between formulations, while in spleen, microspheres of 75:25H resulted more effective. Free drug was quickly eliminated, and accumulated in kidneys, where it could be nephrotoxic. Finally, infection of mice with B. melitensis and treatment with microspheres confirmed the potential of PLGA 75:25H microparticles for the treatment of brucellosis