Enhanced localization of liposomes with prolonged blood circulation time in infected lung tissue.
In an experimental model of unilateral pneumonia caused by Klebsiella pneumoniae in rats we investigated whether intravenous administration of liposomes with prolonged blood circulation time resulted in significant localization of liposomes in infected lung tissue. Liposomes (100 nm) composed of hydrogenated phosphatidylinositol:hydrogenated phosphatidylcholine:cholesterol (molar ratio, 1:10:5) radiolabeled with gallium-67-deferoxamine showed relatively long blood circulation time. The degree of localization of these long circulating liposomes in the infected left lung was significantly higher compared to that of localization of 110 nm egg phosphatidylglycerol:egg phosphatidylcholine:cholesterol (molar ratio, 1:10:5) liposomes which exhibited relatively short blood circulation time. At 16 h after administration of the long circulating liposomes (when 10% of the injected dose was still present in the bloodstream) localization of liposomes in the infected left lung was increased up to 10-fold compared to the left lung of uninfected rats, and appeared to be highly correlated with the intensity of the infection. In the uninfected right lung the localization of long circulating liposomes was not increased. The degree of localization of liposomes in the infected tissue is dependent on the residence time of liposomes in the blood compartment. The extent of localization of long circulating liposomes in infected tissue appeared to be dependent on the liposomal dose administered.
Bakker-Woudenberg
I A
IA
Department of Clinical Microbiology, Erasmus University, Rotterdam, The Netherlands.
Lokerse
A F
AF
ten Kate
M T
MT
Storm
G
G
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D007710:Klebsiella Infections / Q000378:metabolism* / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000254:growth & development; D008081:Liposomes / Q000493:pharmacokinetics*; D008168:Lung / Q000378:metabolism* / Q000382:microbiology; D011014:Pneumonia / Q000378:metabolism* / Q000382:microbiology; D051381:Rats; D011919:Rats, Inbred Strains; D013047:Specific Pathogen-Free Organisms; D014018:Tissue Distribution
D008081:Liposomes