DRUG TARGETING BY POLYALKYLCYANOACRYLATE NANOPARTICLES IS NOT EFFICIENT AGAINST PERSISTENT SALMONELLA

Purpose. We have investigated the efficacy of colistin and ciprofloxac in, free or bound to polyalkylcyanoacrylate nanoparticles, for the tar geting and eradication of Salmonella persisting in the organs of the m ononuclear phagocyte system. Methods. A model of persistent S. typhimu rium infection was developed in C57BL/6 mice using IV inoculation of t he plasmid-cured strain C53. Results. In vivo and ex vivo experiments showed that the persisting bacteria seem to evolve to a nongrowing sta te during experimental salmonellosis. In vivo treatment with free or n anoparticle-bound colistin did not significantly reduce the number of viable Salmonella C53, either in the liver or the spleen of infected m ice. In contrast, in vivo treatment with ciprofloxacin led to a signif icant decrease of bacterial counts in the liver whatever the stage of infection and the form used. However. none of the treatments were able to sterilize the spleen or the liver In ex vivo experiments, colistin was only active against bacteria recovered during the early phase of infection, whereas ciprofloxacin exerted its activity at all times pos tinfection. Conclusions. We suggest that the micro-environment in whic h the bacterial cells persist in vivo probably causes dramatic changes in their susceptibility to antimicrobial agents.