R M Schiffelers1, G Storm, I A Bakker-Woudenberg. 1. Department of Medical Microbiology & Infectious Diseases, Erasmus University Medical Center Rotterdam, The Netherlands. schiffelers@kmic.fgg.eur.nl
Abstract
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 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.
PURPOSE: To gain insight into the host factors influencing liposome localization at sites of bacterial infection. METHODS: In a unilateral Klebsiella pneumoniae pneumoniarat 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 leukopenicrats 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.
Authors: E T Dams; W J Oyen; O C Boerman; G Storm; P Laverman; E B Koenders; J W van der Meer; F H Corstens Journal: J Nucl Med Date: 1998-12 Impact factor: 10.057
Authors: Raymond M Schiffelers; Josbert M Metselaar; Marcel H A M Fens; Adriënne P C A Janssen; Grietje Molema; Gert Storm Journal: Neoplasia Date: 2005-02 Impact factor: 5.715
Authors: Irma A J M Bakker-Woudenberg; Marian T ten Kate; Luke Guo; Peter Working; Johan W Mouton Journal: Antimicrob Agents Chemother Date: 2002-08 Impact factor: 5.191
Authors: J M Metselaar; W B van den Berg; A E M Holthuysen; M H M Wauben; G Storm; P L E M van Lent Journal: Ann Rheum Dis Date: 2004-04 Impact factor: 19.103