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Antibacterial activity of liposome-entrapped ampicillin in vitro and in vivo in relation to the lipid composition

IA Bakker-Woudenberg, AF Lokerse and FH Roerdink

Department of Clinical Microbiology and Antimicrobial Therapy, Erasmus University Rotterdam, The Netherlands.

The antibacterial activity of liposome-entrapped ampicillin against Listeria monocytogenes was investigated in relation to the lipid composition of the liposomes. This was studied in vitro in mouse peritoneal macrophages infected with L. monocytogenes, as well as in vivo in experimental L. monocytogenes infection in mice. Two types of liposomes, a relatively fluid type, consisting of cholesterol- phosphatidylcholine-phosphatidylserine (5:4:1), and a less fluid type, consisting of cholesterol-distearoylphosphatidylcholine- dipalmitoylphosphatidylglyc erol (10:10:1), were used. The uptake of both types of liposomes by macrophages in vitro was similar. However, the rate of intracellular degradation appeared to be dependent on the lipid composition. A correlation was found between the relatively slow degradation of the less fluid liposomes and a delayed intracellular release of the encapsulated ampicillin, as reflected in absent or delayed intracellular killing of L. monocytogenes in vitro. The results obtained in vitro were confirmed by the observations in vivo. Slow degradation of the less fluid liposomes in vivo resulted in a decrease in the therapeutic effect of the antibiotic.

Volume 251, Issue 1, pp. 321-327, 10/01/1989
Copyright © 1989 by American Society for Pharmacology and Experimental Therapeutics




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Copyright © 1989 by the American Society for Pharmacology and Experimental Therapeutics.