Host factors influencing the preferential localization of sterically stabilized liposomes in Klebsiella pneumoniae-infected rat lung tissue.
OBJECTIVE
To gain insight into the host factors influencing liposome localization at sites of bacterial infection.


METHODS
In a unilateral Klebsiella pneumoniae pneumonia rat model, capillary permeability and number of circulating leukocytes was quantified and related to the degree of liposome target localization.


RESULTS
Liposome localization was highest in the hemorrhagic zone of infection, a zone characterized by markedly increased capillary permeability and high bacterial numbers. Both liposome localization and capillary permeability correlated positively with severity of infection. Lung instillation of other inflammatory stimuli, such as lipopolysaccharide or 0.1 M HCl inducing increased capillary permeability, also promoted liposome localization. As liposomal target localization in leukopenic rats was similar to that in immunocompetent rats, contribution of circulating leukocytes seems limited. Intrapulmonary distribution of liposomes shows that leukocytes at the target site are involved in liposome uptake after extravasation.


CONCLUSIONS
Increased capillary permeability plays a crucial role in liposome localization at the infected site, whereas contribution of leukocytes is limited. These results suggest inflammatory conditions that could benefit from liposomal drug delivery. The involvement of leukocytes in liposome uptake at the target site could be important information in the selection of appropriate drugs.
Schiffelers
R M
RM
Department of Medical Microbiology & Infectious Diseases, Erasmus University Medical Center Rotterdam, The Netherlands. schiffelers@kmic.fgg.eur.nl
Storm
G
G
Bakker-Woudenberg
I A
IA
D000818:Animals; D002199:Capillary Permeability; D005070:Evans Blue / Q000493:pharmacokinetics; D017979:Gold Colloid / Q000493:pharmacokinetics; D007710:Klebsiella Infections / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D007711:Klebsiella pneumoniae / Q000378:metabolism*; D008081:Liposomes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics; D051381:Rats; D012997:Solvents / Q000008:administration & dosage / Q000493:pharmacokinetics
D017979:Gold Colloid; D008081:Liposomes; D012997:Solvents; D011092:Polyethylene Glycols; D005070:Evans Blue