title: Potential role of the low-density lipoprotein receptor family as mediators of cellular drug uptake.
abstract: We highlight the importance of the low-density lipoprotein (LDL) receptor family and its pharmaceutical implications in the field of drug delivery. The members of the LDL receptor family are a group of cell surface receptors that transport a number of macromolecules into cells through a process called receptor-mediated endocytosis. This process involves the receptor recognizing a ligand from the extracellular membrane (ECM), internalizing it through clathrin-coated pits and degrading it upon fusion with lysosomes. There are nine members of the receptor family, which include the LDL receptor, low-density lipoprotein-related protein (LRP), megalin, very low-density lipoprotein (VLDL) receptor, apoER2 and sorLA/LRP11, LRP1b, MEGF7, LRP5/6; the former six having been identified in humans. Each member is expressed in a number of different tissues and has a wide range of different ligands, not specific to the recognition of the LDL particle. Thus, rather than the original hypothesis that the receptor is only a mediator of cholesterol uptake, it may also be involved in a number of other physiological functions, including the progression of certain disease states and, potentially, cellular drug uptake. A number of studies have suggested that the LDL receptors are involved in endocytosis of drugs and drug formulations including aminoglycosides, anionic liposomes and cyclosporine A (CsA). This article reviews the importance of lipoproteins as a drug delivery system and how LDL receptors are relevant to the design and targeting of specific drugs.
authors.affiliation: Faculty of Pharmaceutical Sciences, Division of Pharmaceutics and Biopharmaceutics, University of British Columbia, 2146 East Mall Ave., Vancouver, BC, Canada V6T 1Z3.
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Chung
authors.forename: Kishor M
authors.initials: KM
authors.lastname: Wasan
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011485:Protein Binding; D011973:Receptors, LDL / Q000378:metabolism*
chemical_list: D004337:Drug Carriers; D008074:Lipoproteins; D004364:Pharmaceutical Preparations; D011973:Receptors, LDL