Host factors influencing the preferential localization of sterically stabilized liposomes in Klebsiella pneumoniae-infected rat lung tissue

Purpose. 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 localiza-tion. 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 in-fection. Lung instillation of other inflammatory stimuli, such as lipo-polysaccharide or 0.1 M HCl inducing increased capillary permeabil-ity, also promoted liposome localization. As liposomal target local-ization in leukopenic rats was similar to that in immunocompetent rats, contribution of circulating leukocytes seems limited. Intrapul-monary 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. KEY WORDS: inflammatory response; Klebsiella pneumoniae; leu-kocytes; liposomes; pneumonia; rat