Intraphagocytic Killing of Salmonella typhimurium by Liposome-Encapsulated Cephalothin

Abstract

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.

Inhibitory effect of liposome-encapsulated penicillin G on growth of Listeria monocytogenes in mouse macrophages.

“…Therefore, as indicated by Desiderio and Campbell (1983) and also by our results, infections of these bacteria may be favorably treated with these antibiotics if they are administered in liposomeencapsulated forms. This administration method, if proved effective also in vivo, is expected to provide valuable alternatives for the treatment of intracellular bacterial infections.…”

Nanotechnology Tools for Efficient Antibacterial Delivery to Salmonella

“…Liposome formulations of these antibiotics may improve pharmacokinetics and also the targeted delivery to the intracellular infections. In a study with cephalotin, treatment of infected macrophages with multilamellar liposomeencapsulated cephalothin enhanced the intraphagocytic killing of Salmonella typhimurium over that by macrophages treated with free cephalothin (54). Resident murine peritoneal macrophages were shown to be capable of interiorizing the liposome-antibiotic complex leading to a relatively high intracellular concentration of cephalothin.…”

Unilamellar liposomes modulate secretion of tumor necrosis factor by lipopolysaccharide-stimulated macrophages

“…Liposome-encapsulated antibiotics have been shown to have improved penetration into phagocytic cells and have been advocated for use against intracellular microbes (1,22). Indeed, this carrier system augmented the efficacy of various antimicrobial agents against a wide range of microorganisms that survive within macrophages (1,6,9,25). Our laboratory -has previously reported that the use of cefoxitin encapsulated within unilamellar liposomes (95% dipalmitoylphosphatidylcholine, 5% phosphatidylserine) significantly reduced the mortality rate compared with that with the use of free cefoxitin in an intra-abdominal infection model in the rat (5).…”

“…3B. Liposomal encapsulation of antimicrobial agents has proven to be an effective means of drug delivery, particularly against intracellular pathogens (1,9). Phagocytic uptake of liposomes facilitates-exposure of these microorganisms to concentrations of drug which are not normally achieved by incubation of cells with the free antibiotic and results in enhanced microbial killing (25).…”