Targeted delivery of a novel group of site-directed transglutaminase inhibitors to the liver using liposomes: a new approach for the potential treatment of liver fibrosis

J Drug Target. 2011 Sep;19(8):624-31. doi: 10.3109/1061186X.2010.531731. Epub 2010 Nov 11.


Liver fibrosis and its end-stage disease cirrhosis are a main cause of mortality and morbidity worldwide. Thus far, there is no efficient pharmaceutical intervention for the treatment of liver fibrosis. Liver fibrosis is characterized by excessive accumulation of the extracellular matrix (ECM) proteins. Transglutaminase (TG)-mediated covalent cross-linking has been implicated in the stabilization and accumulation of ECM in a number of fibrotic diseases. Thus, the use of tissue TG2 inhibitors has potential in the treatment of liver fibrosis. Recently, we introduced a novel group of site-directed irreversible specific inhibitors of TGs. Here, we describe the development of a liposome-based drug-delivery system for the site-specific delivery of these TG inhibitors into the liver. By using anionic or neutral-based DSPC liposomes, the TG inhibitor can be successfully incorporated into these liposomes and delivered specifically to the liver. Liposomes can therefore be used as a potential carrier system for site-specific delivery of the TG2 inhibitors into the liver, opening up a potential new avenue for the treatment of liver fibrosis and its end-stage disease cirrhosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatography, Gel
  • Drug Carriers / chemistry*
  • Drug Compounding
  • Enzyme Inhibitors / administration & dosage*
  • Enzyme Inhibitors / pharmacokinetics
  • Enzyme Inhibitors / therapeutic use
  • GTP-Binding Proteins / antagonists & inhibitors*
  • Liposomes
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / enzymology
  • Male
  • Mice
  • Molecular Targeted Therapy
  • Organ Specificity
  • Particle Size
  • Phosphatidylcholines / chemistry
  • Phosphatidylserines / chemistry
  • Surface Properties
  • Tissue Distribution
  • Transglutaminases / antagonists & inhibitors*


  • Drug Carriers
  • Enzyme Inhibitors
  • Liposomes
  • Phosphatidylcholines
  • Phosphatidylserines
  • transglutaminase 2
  • Transglutaminases
  • GTP-Binding Proteins