Reprint of: Targeting fibrosis with selective drug carriers☆

Abstract 

This review summarises the progress that has been made in recent years in the field of drug delivery to the hepatic stellate cells (HSCs). HSCs are the crucial cells in the pathogenesis of liver fibrosis and consequently the main target cell for antifibrotic therapies. To enhance cell specificity, such antifibrotic drugs can be coupled to drug carriers that accumulate in this cell type. In recent years, several drug carriers directed at HSCs have become available and many drugs have now been coupled to these carriers. Using this strategy, high drug accumulation in HSCs has been achieved. Several drugs, such as kinase inhibitors, viral vectors, apoptosis-inducing drugs and drugs that inhibit cell proliferation or inflammation, have been targeted to HSCs. Receptor-mediated endocytosis subsequently leads to the release of internalised drugs and the pharmacological effects of these drugs have been demonstrated in HSCs. The selective delivery of drugs to HSCs may therefore provide a new approach to study crucial pathways or new treatments in liver fibrosis. This method may also be applied to those drugs whose adverse effects have prevented their systemic application in the past.

Keywords: Liver fibrosis, Drug-targeting, Antifibrotic drugs, Toxicity, Side effects, Hepatic stellate cells