Fluorescent Cell-Traceable Dexamethasone-Loaded Liposomes for the Treatment of Inflammatory Liver Diseases

Biomaterials. 2015 Jan;37:367-82. doi: 10.1016/j.biomaterials.2014.10.030. Epub 2014 Oct 26.

Abstract

Liposomes are routinely used carrier materials for delivering drug molecules to pathological sites. Besides in tumors and inflammatory sites, liposomes also strongly accumulate in liver and spleen. The potential of using liposomes to treat acute and chronic liver disorders, however, has not yet been evaluated. We here explored the therapeutic potential of dexamethasone (Dex)-loaded liposomes for inflammatory liver diseases, using experimental models of acute and chronic liver injury in mice. Fluorescently labeled liposomes predominantly accumulated in hepatic phagocytes, but also in T cells. Importantly, Dex-loaded liposomes reduced T cells in blood and liver, more effectively than free Dex, and endorsed the anti-inflammatory polarization of hepatic macrophages. In experimental chronic liver damage, Dex-loaded liposomes significantly reduced liver injury and liver fibrosis. In immune-mediated acute hepatitis Dex-loaded liposomes, but not free Dex, significantly reduced disease severity. T cells, not macrophages, were significantly depleted by Dex liposomes in liver disease models in vivo, as further supported by mechanistic cell death in vitro studies. Our data indicate that Dex liposomes may be an interesting treatment option for liver diseases, in particular for immune-mediated hepatitis. The depletion of T cells might represent the major mechanism of action of Dex liposomes, rather than their macrophage-polarizing activities.

Keywords: Dexamethasone; Liposomes; Liver fibrosis; Liver injury; Macrophages; T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Death / drug effects
  • Cell Survival / drug effects
  • Dexamethasone / administration & dosage
  • Dexamethasone / pharmacology
  • Dexamethasone / therapeutic use*
  • Fluorescence
  • Hepatitis / drug therapy
  • Hepatitis / pathology
  • Immunomodulation / drug effects
  • Immunosuppression
  • Inflammation / drug therapy*
  • Inflammation / pathology
  • Liposomes
  • Liver / drug effects
  • Liver / immunology
  • Liver / pathology
  • Liver Cirrhosis / drug therapy
  • Liver Cirrhosis / pathology
  • Liver Diseases / complications
  • Liver Diseases / drug therapy*
  • Liver Diseases / pathology
  • Mice, Inbred C57BL
  • Organ Specificity / drug effects
  • T-Lymphocytes / drug effects
  • Tissue Distribution / drug effects

Substances

  • Liposomes
  • Dexamethasone