title: Carbohydrate-based materials for targeted delivery of drugs and genes to the liver.
abstract: The insult to liver by toxic materials leads to cirrhosis, hepatitis and cancer. Upon administration, drugs accumulate in liver, which is systemically cleared by reticuloendothelial system. However, specific targeting of drugs to liver is a serious challenge. Specific delivery of molecules to hepatocytes is accomplished by targeting cell surface lectins, asialoglycoprotein receptors. Asialofetuin, N-acetyl glucosamine and galactose are high-affinity ligands of asialoglycoprotein receptors. The bioconjugation of drugs, fluorescent molecules and gene delivery vectors with lectin-targeting agents, and their delivery in liver hepatocytes, is discussed. Mannose and N-acetyl glucosamine conjugates are evaluated for their delivery to hepatic stellate and kupffer cells. The glycosylated gene and drug delivery vectors in clinical trials are outlined.
authors.affiliation: Chemical Engineering, California Institute of Technology, 1200 E California Blvd, Pasadena, CA 91125, USA.
authors.forename: Marya
authors.initials: M
authors.lastname: Ahmed
authors.affiliation: Chemical & Materials Engineering, University of Alberta, 116 St & 85 Ave, Edmonton, AB T6G 2R3, Canada.
authors.forename: Ravin
authors.initials: R
authors.lastname: Narain
mesh_terms: D000117:Acetylglucosamine / Q000737:chemistry; D000818:Animals; D001212:Asialoglycoproteins / Q000737:chemistry; D002241:Carbohydrates / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D060748:Fetuins / Q000737:chemistry; D005690:Galactose / Q000737:chemistry; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism*
chemical_list: D001212:Asialoglycoproteins; D002241:Carbohydrates; D060748:Fetuins; C017029:asialofetuin; D000117:Acetylglucosamine; D005690:Galactose
keywords: N-acetyl galactosamine-modified nanoparticles; N-acetyl glucosamine-modified nanoparticles; asialoglycoprotein receptor; galactosylated nanoparticles; glycolipids; glycopolymers; glycyrrhetinic acid-modified nanoparticles; liver targeting; mannosylated nanoparticles