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

Pharm Res. 2001 Jun;18(6):780-7. doi: 10.1023/a:1011080211226.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Capillary Permeability
  • Evans Blue / pharmacokinetics
  • Gold Colloid / pharmacokinetics
  • Klebsiella Infections / drug therapy*
  • Klebsiella Infections / metabolism*
  • Klebsiella Infections / pathology
  • Klebsiella pneumoniae / metabolism*
  • Liposomes / administration & dosage
  • Liposomes / pharmacokinetics*
  • Lung / metabolism*
  • Lung / pathology
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / pharmacokinetics
  • Rats
  • Solvents / administration & dosage
  • Solvents / pharmacokinetics

Substances

  • Gold Colloid
  • Liposomes
  • Solvents
  • Polyethylene Glycols
  • Evans Blue