Treatment of experimental salmonellosis in mice with ampicillin-bound nanoparticles.
We tested the effectiveness of ampicillin bound to nanoparticles of polyisohexylcyanoacrylate (PIHCA) in treating C57BL/6 mice experimentally infected with Salmonella typhimurium C5. The diameter of the nanoparticles was 187 +/- 13 nm, and the ampicillin/PIHCA ratio was 0.2/1. The proportion of ampicillin bound was 90 +/- 3%. All control mice and all those treated with nonloaded nanoparticles died within 10 days of infection. By contrast, all mice treated with a single injection of 0.8 mg of nanoparticle-bound ampicillin survived. With free ampicillin, a similar curative effect required three doses of 32 mg each. Lower doses delayed but did not reduce mortality. The sharp increase in the therapeutic index of ampicillin after linkage to PIHCA nanoparticles was explained by studies of the distribution of ampicillin, which showed that when bound to nanoparticles, the ampicillin was concentrated mainly in the liver and spleen, the primary foci of infection in the experimental model that we used. These findings warrant further development of intracellular targeting of antibiotics on biodegradable polymeric carriers such as PIHCA.
Fattal
E
E
Laboratoire de Pharmacie Galénique et de Biopharmacie, U.A. Centre National de la Recherche Scientifique 1218, Université de Paris XI, France.
Youssef
M
M
Couvreur
P
P
Andremont
A
A
D000667:Ampicillin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D002626:Chemistry, Pharmaceutical; D008081:Liposomes; D008099:Liver / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D012481:Salmonella Infections, Animal / Q000188:drug therapy* / Q000382:microbiology; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D013154:Spleen / Q000378:metabolism / Q000382:microbiology; D014018:Tissue Distribution
D008081:Liposomes; D000667:Ampicillin