title: Pathways of protein and lipid receptor-mediated transcytosis in drug delivery.
abstract: A critical factor for the efficacy of drugs is their availability at the site of interest. However, crossing endothelial and epithelial cell layers like the blood-brain barrier and the blood-intestinal barrier represents a major bottleneck for drug targeting. Coupling drugs to carriers that recognize endogenous receptors, which are then transported through cell layers by transcytosis, is a promising approach to overcome this bottleneck. Areas covered: This review focuses on the intracellular pathways of receptor-mediated transcytosis and their applicability for transcellular drug delivery. It gives an overview about transcytotic trafficking routes in epithelia and highlights the well-studied examples of immungobulin transcytosis and transferrin transcytosis. The current knowledge about the less understood transcytosis pathways in endothelia is also summarized and low-density lipoprotein transcytosis is described. In addition, transcytosis pathways that are based on glycosphingolipids and lectins as their receptors are presented. Expert opinion: Multiple transcellular drug delivery approaches based on proteinaceous receptors have been developed in recent years, whereas lectins that bind to glycosphingolipids emerge as promising alternative. Closer investigation of endogenous transcytosis mechanisms, especially in endothelia, will be a fruitful endeavor to devise more optimized carriers for transcytotic drug delivery.
authors: a Faculty of Biology , Albert-Ludwigs-University Freiburg , Freiburg , Germany.|b BIOSS Centre for Biological Signalling Studies , Albert-Ludwigs-University Freiburg , Freiburg , Germany.
authors: Roland
authors: R
authors: Thuenauer
authors: a Faculty of Biology , Albert-Ludwigs-University Freiburg , Freiburg , Germany.|b BIOSS Centre for Biological Signalling Studies , Albert-Ludwigs-University Freiburg , Freiburg , Germany.
authors: Stefan K
authors: SK
authors: Müller
authors: a Faculty of Biology , Albert-Ludwigs-University Freiburg , Freiburg , Germany.|b BIOSS Centre for Biological Signalling Studies , Albert-Ludwigs-University Freiburg , Freiburg , Germany.
authors: Winfried
authors: W
authors: Römer
mesh_terms: D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism; D016503:Drug Delivery Systems; D004727:Endothelium / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D008055:Lipids / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D057900:Transcytosis; D014168:Transferrin / Q000378:metabolism
chemical_list: D008055:Lipids; D004364:Pharmaceutical Preparations; D014168:Transferrin
keywords: Blood-brain barrier; Shiga toxin; glycosphingolipids; intracellular trafficking; lectins; polarized epithelial cells