Drug targeting by polyalkylcyanoacrylate nanoparticles is not efficient against persistent Salmonella.
OBJECTIVE
We have investigated the efficacy of colistin and ciprofloxacin, free or bound to polyalkylcyanoacrylate nanoparticles, for the targeting and eradication of Salmonella persisting in the organs of the mononuclear phagocyte system.


METHODS
A model of persistent S. typhimurium infection was developed in C57BL/6 mice using i.v. inoculation of the plasmid-cured strain C53.


RESULTS
In vivo and ex vivo experiments showed that the persisting bacteria seem to evolve to a nongrowing state during experimental salmonellosis. In vivo treatment with free or nanoparticle-bound colistin did not significantly reduce the number of viable Salmonella C53, either in the liver or the spleen of infected mice. In contrast, in vivo treatment with ciprofloxacin led to a significant 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 postinfection.


CONCLUSIONS
We suggest that the micro-environment in which the bacterial cells persist in vivo probably causes dramatic changes in their susceptibility to antimicrobial agents.
Page-Clisson
M E
ME
Laboratoire de Pharmacie Galénique et de Biopharmacie, Centre National de la Recherche Scientifique, URA 1218, Université de Paris XI, Châtenay-Malabry, France.
Pinto-Alphandary
H
H
Chachaty
E
E
Couvreur
P
P
Andremont
A
A
D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000493:pharmacokinetics / Q000494:pharmacology*; D003091:Colistin / Q000493:pharmacokinetics / Q000494:pharmacology*; D003487:Cyanoacrylates; D004337:Drug Carriers; D005260:Female; D008099:Liver / Q000187:drug effects / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D010316:Particle Size; D012481:Salmonella Infections, Animal / Q000188:drug therapy* / Q000382:microbiology; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics; D013154:Spleen / Q000187:drug effects / Q000382:microbiology
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D003487:Cyanoacrylates; D004337:Drug Carriers; D002939:Ciprofloxacin; D003091:Colistin