Pharmaceutical Research

, Volume 18, Issue 6, pp 780–787

Host Factors Influencing the Preferential Localization of Sterically Stabilized Liposomes in Klebsiella Pneumoniae-Infected Rat Lung Tissue

  • R. M. Schiffelers
  • G. Storm
  • I. A. J. M. Bakker-Woudenberg
Article

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.

inflammatory response Klebsiella pneumoniae leukocytes liposomes pneumonia rat 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

REFERENCES

  1. 1.
    A. J. Schroit, J. Madsen, and R. Nayar. R. Liposome-cell interactions: In vitro discrimination of uptake mechanism and in vivo targeting strategies to mononuclear phagocytes. Chem. Phys. Lipids 40:373-393 (1986).Google Scholar
  2. 2.
    R. Kirsh and G. Poste. Liposome targeting to macrophages: Opportunities for treatment of infectious diseases. Adv. Exp. Med. 202:171-184 (1986).Google Scholar
  3. 3.
    G. Storm and D. J. A. Crommelin. Liposomes-Quo vadis? Pharm. Sci. Technol. Today 1:19-31 (1998).Google Scholar
  4. 4.
    M. C. Woodle, M. S. Newman, and P. K. Working. Biological properties of sterically stabilized liposomes. In D. Lasic and F. J. Martin (eds.), Stealth Liposomes, CRC Press, Boca Raton, 1995 pp. 103-117.Google Scholar
  5. 5.
    G. Storm and M. C. Woodle. Long circulating liposomes: from concept to clinical reality. In M. C. Woodle and G. Storm (eds.), Long Circulating Liposomes: Old Drugs, New Therapeutics, Springer Verlag, Germany, 1998 pp. 3-16.Google Scholar
  6. 6.
    T. M. Allen. Liposomes: Opportunities in drug delivery. Drugs 54S1:8-14, (1997).Google Scholar
  7. 7.
    V. Rousseau, B. Denizot, J. J. Le Jeune, and P. Jallet. Early detection of liposome brain localization in rat experimental allergic encephalomyelitis. Exp. Brain Res. 125:255-264 (1999).Google Scholar
  8. 8.
    S. K. Klimuk, S. C. Semple, P. Scherrer, and M. J. Hope. Contact hypersensitivity: A simple model for the characterization of disease-site targeting by liposomes. Biochim. Biophys. Acta 1417:191-201 (1999).Google Scholar
  9. 9.
    E. T. Dams, W. J. Oyen, and O. C. Boerman. Technetium-99m-labeled liposomes to image experimental colitis in rabbits: Comparison with technetium-99m-HMPAO-granulocytes and technetium-99m-HYNIC-IgG. J. Nucl. Med. 39:2172-2178 (1998).Google Scholar
  10. 10.
    V. Awasthi, B. Goins, R. Klipper, R. Loredo, D. Korvick, and W. T. Phillips. Imaging experimental osteomyelitis using radiolabeled liposomes. J. Nucl. Med. 39:1089-1094 (1998).Google Scholar
  11. 11.
    M. L. Corvo, O. C. Boerman, W. J. Oyen, L. van Bloois, M. E. Cruz, D. J. A. Crommelin, and G. Storm. Intravenous administration of superoxide dismutase entrapped in long circulating liposomes. II. In vivo fate in a rat model of adjuvant arthritis. Biochim. Biophys. Acta 1419:325-334 (1999).Google Scholar
  12. 12.
    W. J. Oyen, O. C. Boerman, and G. Storm. Detecting infection and inflammation with technetium-99m-labeled Stealth liposomes. J. Nucl. Med. 37:1392-1397 (1996).Google Scholar
  13. 13.
    I. A. J. M. Bakker-Woudenberg, A. F. Lokerse, M. T. ten Kate, J. W. Mouton, M. C. Woodle, and G. Storm. Liposomes with prolonged blood circulation and selective localization in Klebsiella pneumoniae-infected lung tissue. J. Inf. Dis. 168:164-171 (1993).Google Scholar
  14. 14.
    W. J. Oyen, O. C. Boerman, C. J. van der Laken, R. A. Claessens, J. W. van der Meer, and F. H. Corstens. The uptake mechanisms of inflammation-and infection-localizing agents. Eur. J. Nucl. Med. 23:459-465 (1996).Google Scholar
  15. 15.
    I. A. J. M. Bakker-Woudenberg, M. T. ten Kate, L. E. T. Stearne-Cullen, and M. C. Woodle. Efficacy of gentamicin or ceftazidime entrapped in liposomes with prolonged blood circulation and enhanced localization in Klebsiella pneumoniae-infected lung tissue. J. Inf. Dis. 171:938-947 (1995).Google Scholar
  16. 16.
    C. A. Owen and E. J. Campbell. The cell biology of leukocyte-mediated proteolysis. J. Leukoc. Biol. 65:137-150 (1999).Google Scholar
  17. 17.
    I. A. J. M. Bakker-Woudenberg, J. C. van den Berg, and M. F. Michel. Therapeutic activities of cefazolin, cefotaxime, and ceftazidime against experimentally induced Klebsiella pneumoniae pneumonia in rats. Antimicrob. Agents Chemother. 22:1042-1050 (1982).Google Scholar
  18. 18.
    A. C. Leenders, S. de Marie, M. T. ten Kate, I. A. J. M. Bakker-Woudenberg, and H. A. Verbrugh. Liposomal amphotericin B (AmBisome) reduces dissemination of infection as compared with amphotericin B deoxycholate (Fungizone) in a rate model of pulmonary aspergillosis. J. Antimicrob. Chemother. 38:215-25 (1996).Google Scholar
  19. 19.
    A. Gabizon, J. Huberty, R. M. Straubinger, and D. Papahadjopoulos. An improved method for in vivo tracing and imaging of liposomes using a gallium 67-deferoxamine complex. J. Lip. Res. 1:123-135 (1988).Google Scholar
  20. 20.
    G. R. J. Bartlett. Phosphorus assay in column chromatography. J. Biol. Chem. 234:466 (1959).Google Scholar
  21. 21.
    W. Zhang, L. Guo, J. A. Nadel, and D. Papahadjopoulos. Inhibition of tracheal vascular extravasation by liposome-encapsulated albuterol in rats. Pharm. Res. 15:455-460 (1998).Google Scholar
  22. 22.
    G. Thurston, T. J. Murphy, P. Baluk, J. R. Lindsey, and D. McDonald. Angiogenesis in mice with chronic airway inflammation: strain-dependent differences. Am. J. Path. 153:1099-1112 (1998).Google Scholar
  23. 23.
    T. Nagase, E. Ohga, and E. Sudo. Intercellular adhesion molecule-1 mediates acid aspiration-induced lung injury. Am. J. Resp. Crit. Care Med. 154:504-510 (1996).Google Scholar
  24. 24.
    J. Kurantsin-Mills, H. M. Jacobs, R. Siegel, M. M. Cassidy, and L. S. Lessin. Indium-111 oxine labeled erythrocytes: Cellular distribution and efflux kinetics of the label. Int. J. Rad. Appl. Instr. B 16:821-827 (1989).Google Scholar
  25. 25.
    T. Daemen, M. Velinova, and J. Regts. Different intrahepatic distribution of phosphatidylglycerol and phosphatidylserine liposomes in the rat. Hepatology 26:416-423 (1997).Google Scholar
  26. 26.
    J. Tamaoki, E. Tagaya, I. Yamawaki, N. Sakai, A. Nagai, and K. Konno. Effect of erythromycin on endotoxin-induced microvascular leakage in the rat trachea and lungs. Am. J. Resp. Crit. Care Med. 151:1582-1588 (1995).Google Scholar
  27. 27.
    E. T. Dams, M. J. Becker, W. J. Oyen, O. C. Boerman, G. Storm, P. Laverman, S. de Marie, J. W. van der Meer, I. A. J. M. Bakker-Woudenberg, F. H. Corstens. Scintigraphic imaging of bacterial and fungal infection in granulocytopenic rats. J. Nucl. Med. 40:2066-2072 (1999).Google Scholar
  28. 28.
    B. A. Collin and R. Ramphal. Pneumonia in the compromised host including cancer patients and transplant patients. Inf. Dis. Clin. N. Am. 12:781-805 (1998).Google Scholar
  29. 29.
    S. K. Huang, F. J. Martin, G. Jay, J. Vogel, D. Papahadjopoulos, and D. S. Friend. Extravasation and transcytosis of liposomes in Kaposi's sarcoma-like dermal lesions of transgenic mice bearing the HIV tat gene. Am. J. Path. 143:10-14 (1993).Google Scholar
  30. 30.
    J. Rosenecker, W. Zhang, and K. Hong. Increased liposome extravasation in selected tissues: effect of substance P. Proc. Natl. Acad. Sci. USA 93:7236-7241 (1996).Google Scholar
  31. 31.
    S. K. Huang, F. J. Martin, D. S. Friend, and D. Papahadjopoulos. Mechanism of stealth liposome accumulation in some pathological tissues. In D. Lasic and F. J. Martin (eds.), Stealth Liposomes, CRC press, Boca Raton, 1995 pp. 119-125.Google Scholar

Copyright information

© Plenum Publishing Corporation 2001

Authors and Affiliations

  • R. M. Schiffelers
    • 1
    • 2
  • G. Storm
    • 2
  • I. A. J. M. Bakker-Woudenberg
    • 1
  1. 1.Department of Medical Microbiology & Infectious DiseasesErasmus University Medical Center Rotterdam (EMCR)RotterdamThe Netherlands
  2. 2.Department of PharmaceuticsUtrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht UniversityUtrechtThe Netherlands

Personalised recommendations