Liposomes with prolonged blood circulation and selective localization in Klebsiella pneumoniae-infected lung tissue.
Studies of two types of small liposomes, differing with respect to their lipid composition in terms of bilayer fluidity, charge, and hydrophilicity of the liposomal surface, were done to evaluate their usefulness for delivery of encapsulated therapeutic agents to sites of infection. The liposomes showed substantial localization in infected lung tissue after intravenous administration. This was demonstrated in a model of unilateral Klebsiella pneumoniae pneumonia in rats, in which the left lung was infected but the right lung of the same animal developed no infection. The degree of localization in the infected left lung was different for the two types of liposomes. For the liposome type with the longer blood residence time, containing a surface coating of polyethylene glycol, localization in the infected left lung was dependent on the liposomal dose, correlated with the intensity of infection, and reached 9% of the injected liposomal dose in severely infected rats.
Dept. of Clinical Microbiology, Erasmus University, Rotterdam, Netherlands.
I A
IA
Bakker-Woudenberg
A F
AF
Lokerse
M T
MT
ten Kate
J W
JW
Mouton
M C
MC
Woodle
G
G
Storm
D000818:Animals; D004337:Drug Carriers; D005260:Female; D007710:Klebsiella Infections / Q000097:blood* / Q000473:pathology; D007711:Klebsiella pneumoniae / Q000187:drug effects; D008081:Liposomes / Q000493:pharmacokinetics*; D008168:Lung / Q000098:blood supply / Q000378:metabolism; D011014:Pneumonia / Q000097:blood* / Q000188:drug therapy / Q000382:microbiology; D011092:Polyethylene Glycols / Q000493:pharmacokinetics; D051381:Rats
D004337:Drug Carriers; D008081:Liposomes; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol