Targeted delivery of drugs for liver fibrosis

Expert Opin Drug Deliv. 2009 May;6(5):531-41. doi: 10.1517/17425240902936834.

Abstract

Liver fibrosis and its end stage disease cirrhosis are a major cause of mortality and morbidity around the world. There is no effective pharmaceutical intervention for liver fibrosis at present. Many drugs that show potent antifibrotic activities in vitro often show only minor effects in vivo because of insufficient concentrations of drugs accumulating around the target cell and their adverse effects as a result of affecting other non-target cells. Hepatic stellate cells (HSC) play a critical role in the fibrogenesis of liver, so they are the target cells of antifibrotic therapy. Several kinds of targeted delivery system that could target the receptors expressed on HSC have been designed, and have shown an attractive targeted potential in vivo. After being carried by these delivery systems, many agents showed a powerful antifibrotic effect in animal models of liver fibrosis. These targeted delivery systems provide a new pathway for the therapy of liver fibrosis. The characteristics of theses targeted carriers are reviewed in this paper.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use
  • Dependovirus / metabolism
  • Drug Carriers / chemistry*
  • Drug Carriers / therapeutic use*
  • Drug Delivery Systems / methods*
  • Endothelial Cells / metabolism
  • Genetic Therapy / methods
  • Hepatic Stellate Cells / drug effects*
  • Hepatic Stellate Cells / immunology
  • Hepatic Stellate Cells / metabolism*
  • Humans
  • Kupffer Cells / metabolism
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / immunology
  • Liver Cirrhosis / metabolism*
  • Mannosephosphates / chemistry
  • Mannosephosphates / metabolism
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / metabolism
  • Receptors, Cell Surface / drug effects
  • Receptors, Cell Surface / metabolism
  • Receptors, Platelet-Derived Growth Factor / agonists
  • Receptors, Platelet-Derived Growth Factor / metabolism
  • Serum Albumin / chemistry
  • Serum Albumin / metabolism
  • Synaptophysin / immunology

Substances

  • Antibodies, Monoclonal
  • Drug Carriers
  • Mannosephosphates
  • Peptides, Cyclic
  • Receptors, Cell Surface
  • Serum Albumin
  • Synaptophysin
  • cyclic arginine-glycine-aspartic acid peptide
  • retinol binding protein receptor
  • mannose-6-phosphate
  • Receptors, Platelet-Derived Growth Factor