Liposome-incorporated ciprofloxacin in treatment of murine salmonellosis.
We used a dehydration-rehydration procedure in order to efficiently incorporate ciprofloxacin into phospholipid vesicles (liposomes), which we then used to treat BALB/c mice that had been infected per os with Salmonella dublin. A single injection of liposome-incorporated ciprofloxacin (LIC) was 10 times more effective than a single injection of free drug at preventing mortality. When free ciprofloxacin was administered twice daily for 5 days, it was more effective than when it was administered as a single dose. Treatment with LIC produced dose-dependent decreases in bacterial counts in spleen, stool, and Peyer's patches, indicating that the drug had distributed to all areas of inflammation, not just to the major reticuloendothelial system organs. Although LIC was cleared rapidly from the blood, drug persisted in the liver and spleen for at least 48 h after administration of a dose of LIC. We attribute the enhanced activity of LIC to the concentration and persistence of active drug in the infected organs. Our results confirm the fact that ciprofloxacin is effective therapy for systemic salmonella infection and show that LIC is even more effective than aqueous ciprofloxacin in our model.
Magallanes
M
M
Department of Medicine and Pathology, University of California San Diego School of Medicine, La Jolla 92093.
Dijkstra
J
J
Fierer
J
J
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002939:Ciprofloxacin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004337:Drug Carriers; D005260:Female; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D012481:Salmonella Infections, Animal / Q000188:drug therapy* / Q000382:microbiology
D004337:Drug Carriers; D008081:Liposomes; D002939:Ciprofloxacin