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  • Title: Potential role of the low-density lipoprotein receptor family as mediators of cellular drug uptake.
    Author: Chung NS, Wasan KM.
    Journal: Adv Drug Deliv Rev; 2004 May 07; 56(9):1315-34. PubMed ID: 15109771.
    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.
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