title: Surface charge of nanoparticles determines their endocytic and transcytotic pathway in polarized MDCK cells.
abstract: A major challenge in drug delivery is the internalization through the apical plasma membrane of the polarized epithelial cells lining organs facing the external environment, e.g., lungs and the gastrointestinal tract. The reduced permeation of drugs entering through this pathway is in part due to the mucosal barrier and low rate of endocytosis at these membranes. We investigated the possible role of nanoparticle surface charge on its entry through the apical plasma membrane and its intracellular pathway. We found that both cationic and anionic nanoparticles are targeted mainly to the clathrin endocytic machinery. A fraction of both nanoparticle formulations is suspected to internalize through a macropinocytosis-dependent pathway. A significant amount of nanoparticles transcytose and accumulate at the basolateral membrane. Some anionic but not cationic nanoparticles transited through the degradative lysosomal pathway. Taken together, these observations indicate that cationic nanoparticles, in addition to their potential for drug delivery to epithelia, may be promising carriers for transcytosing drugs to the blood stream.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, The Hebrew University of Jerusalem, POB 12065, Jerusalem 91120, Israel.
authors.forename: Oshrat
authors.initials: O
authors.lastname: Harush-Frenkel
authors.forename: Eva
authors.initials: E
authors.lastname: Rozentur
authors.forename: Simon
authors.initials: S
authors.lastname: Benita
authors.forename: Yoram
authors.initials: Y
authors.lastname: Altschuler
mesh_terms: D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D016764:Cell Polarity / Q000187:drug effects / Q000502:physiology*; D004285:Dogs; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D013499:Surface Properties