TY - JOUR
T1 - Drug targeting to the diseased liver
AU - Poelstra, Klaas
AU - Prakash, Jai
AU - Beljaars, Leonie
PY - 2012/7/20
Y1 - 2012/7/20
N2 - Many serious liver diseases affecting millions of people world-wide cannot be treated despite many efforts which warrants a search for new therapeutic strategies. Potent drugs may not be effective enough in vivo or exhibit adverse effects and enhanced delivery into the target cells may improve this significantly. We aim to summarize the available options for drug delivery to the different intrahepatic cell-types. The most relevant target cells are identified for each liver disease and the strategies for drug delivery to these cells are subsequently reviewed. The review describes the use of proteins, viruses, polymers and liposomes for therapeutic purposes in various liver diseases. It is shown that to date, all resident intrahepatic cells can be reached with several different drug carriers. Much progress has been made in recent years to deliver small drug molecules, proteins and nucleic acids specifically to the key pathogenic cells in vivo. The knowledge of drug targeting gained in the past decades, combined with a proper preclinical evaluation, may bring new therapeutics to the clinic in the near future. (C) 2012 Elsevier B.V. All rights reserved.
AB - Many serious liver diseases affecting millions of people world-wide cannot be treated despite many efforts which warrants a search for new therapeutic strategies. Potent drugs may not be effective enough in vivo or exhibit adverse effects and enhanced delivery into the target cells may improve this significantly. We aim to summarize the available options for drug delivery to the different intrahepatic cell-types. The most relevant target cells are identified for each liver disease and the strategies for drug delivery to these cells are subsequently reviewed. The review describes the use of proteins, viruses, polymers and liposomes for therapeutic purposes in various liver diseases. It is shown that to date, all resident intrahepatic cells can be reached with several different drug carriers. Much progress has been made in recent years to deliver small drug molecules, proteins and nucleic acids specifically to the key pathogenic cells in vivo. The knowledge of drug targeting gained in the past decades, combined with a proper preclinical evaluation, may bring new therapeutics to the clinic in the near future. (C) 2012 Elsevier B.V. All rights reserved.
KW - Drug carriers
KW - Drug targeting
KW - Liver fibrosis
KW - Hepatic inflammation
KW - Hepatocellular carcinoma
KW - HEPATIC STELLATE CELLS
KW - PRIMARY BILIARY-CIRRHOSIS
KW - DUCT-LIGATED RATS
KW - HUMAN HEPATOCELLULAR-CARCINOMA
KW - TRIPLEX-FORMING OLIGONUCLEOTIDES
KW - SINUSOIDAL ENDOTHELIAL-CELLS
KW - TO-MESENCHYMAL TRANSITION
KW - MEDIATED GENE-TRANSFER
KW - BOVINE SERUM-ALBUMIN
KW - POLY-L-LYSINE
U2 - 10.1016/j.jconrel.2012.02.011
DO - 10.1016/j.jconrel.2012.02.011
M3 - Review article
SN - 0168-3659
VL - 161
SP - 188
EP - 197
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 2
ER -