Targeted delivery of drugs for liver fibrosis.
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.
Zhongshan Hospital Affiliated to Fudan University, Department of Gastroenterology, 180 Fenglin Road, Shanghai, China. lifeng197881@yahoo.com.cn
Feng
F
Li
Ji-yao
JY
Wang
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000229:Dependovirus / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry* / Q000627:therapeutic use*; D016503:Drug Delivery Systems / Q000379:methods*; D042783:Endothelial Cells / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007728:Kupffer Cells / Q000378:metabolism; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism*; D008360:Mannosephosphates / Q000737:chemistry / Q000378:metabolism; D010456:Peptides, Cyclic / Q000737:chemistry / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000819:agonists / Q000378:metabolism; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism; D016708:Synaptophysin / Q000276:immunology
D000911:Antibodies, Monoclonal; D004337:Drug Carriers; D008360:Mannosephosphates; D010456:Peptides, Cyclic; D011956:Receptors, Cell Surface; D012709:Serum Albumin; D016708:Synaptophysin; C507169:cyclic arginine-glycine-aspartic acid peptide; C027928:retinol binding protein receptor; C027693:mannose-6-phosphate; D017479:Receptors, Platelet-Derived Growth Factor