Targeting hepatic stellate cells for cell-specific treatment of liver fibrosis.
Since hepatic stellate cells (HSC) play a crucial role in the development of liver fibrosis, this cell is the major target for anti-fibrotic drugs. Most of the experimental drugs that influenced the HSC activity showed however low efficacy in vivo. Either a low uptake of the compounds in the cells that cause disease might account for this lack of effect, or side-effects in other cells may limit the dosage of the drugs. These side-effects may even counteract the beneficial effects. Therefore a selective delivery of drugs to the HSC may comprise a promising new way to improve liver fibrosis. The targeting to HSC has become a feasible option, because albumin-based carriers have been developed that preferentially distribute to HSC in fibrotic rat livers. In addition to the targeting of drugs, also the selective delivery of genes to HSC in fibrotic livers is of interest for therapeutic purposes and a start is made in this respect. The present review discusses the drugs to be targeted to HSC and summarizes some of the problems encountered during this novel strategy in the treatment of liver fibrosis.
Beljaars
Leonie
L
Groningen University Institute for Drug Exploration, Dept. of Pharmacokinetics and Drug Delivery, University Center for Pharmacy, Groningen, The Netherlands. L.Beljaars@farm.rug.nl
Meijer
Dirk K F
DK
Poelstra
Klaas
K
D000818:Animals; D016207:Cytokines / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods; D005912:Gliotoxin / Q000008:administration & dosage; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000378:metabolism / Q000628:therapy; D008954:Models, Biological; D010431:Pentoxifylline / Q000008:administration & dosage
D016207:Cytokines; D005912:Gliotoxin; D010431:Pentoxifylline