Intraphagocytic killing of Salmonella typhimurium by liposome-encapsulated cephalothin.
Multilamellar liposomes (lipid bilayer vesicles) composed of phosphatidylcholine, cholesterol, and phosphatidylserine (molar ratio, 6:3:1) were produced and then made to entrap an aqueous solution of cephalothin. Resident murine peritoneal macrophages were shown to be capable of interiorizing the liposome-antibiotic complex; this event resulted in a relatively high intracellular concentration of cephalothin. In macrophages infected in vitro with Salmonella typhimurium, intracellular killing of the bacteria was maximal at 60 min of incubation; at this time, 60% of the interiorized organisms had been killed. Treatment of infected macrophages with liposome-encapsulated cephalothin enhanced the intraphagocytic killing of S typhimurium over that by macrophages treated with free cephalothin. These results demonstrate the superiority of liposome-encapsulated antibiotics to free antibiotics in effecting the elimination of a facultative intracellular bacterium from its intracellular site. This type of complex may find application in the treatment of diseases caused by this group of microorganisms.
D000818:Animals; D002512:Cephalothin / Q000494:pharmacology*; D004705:Endocytosis; D008081:Liposomes / Q000008:administration & dosage*; D008264:Macrophages / Q000382:microbiology*; D051379:Mice; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000502:physiology
D008081:Liposomes; D002512:Cephalothin