Drug Flux Across RPE Cell Models : The Hunt for An Appropriate Outer Blood-Retinal Barrier Model for Use in Early Drug Discovery

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Hellinen , L , Hongisto , H , Ramsay , E , Kaarniranta , K , Vellonen , K-S , Skottman , H & Ruponen , M 2020 , ' Drug Flux Across RPE Cell Models : The Hunt for An Appropriate Outer Blood-Retinal Barrier Model for Use in Early Drug Discovery ' , Pharmaceutics , vol. 12 , no. 2 , 176 . https://doi.org/10.3390/pharmaceutics12020176

Title: Drug Flux Across RPE Cell Models : The Hunt for An Appropriate Outer Blood-Retinal Barrier Model for Use in Early Drug Discovery
Author: Hellinen, Laura; Hongisto, Heidi; Ramsay, Eva; Kaarniranta, Kai; Vellonen, Kati-Sisko; Skottman, Heli; Ruponen, Marika
Contributor: University of Helsinki, Drug Delivery Unit
Date: 2020-02
Language: eng
Number of pages: 13
Belongs to series: Pharmaceutics
ISSN: 1999-4923
URI: http://hdl.handle.net/10138/314142
Abstract: The retinal pigment epithelial (RPE) cell monolayer forms the outer blood-retinal barrier and has a crucial role in ocular pharmacokinetics. Although several RPE cell models are available, there have been no systematic comparisons of their barrier properties with respect to drug permeability. We compared the barrier properties of several RPE secondary cell lines (ARPE19, ARPE19mel, and LEPI) and both primary (hfRPE) and stem-cell derived RPE (hESC-RPE) cells by investigating the permeability of nine drugs (aztreonam, ciprofloxacin, dexamethasone, fluconazole, ganciclovir, ketorolac, methotrexate, voriconazole, and quinidine) across cell monolayers. ARPE19, ARPE19mel, and hfRPE cells displayed a narrow P-app value range, with relatively high permeation rates (5.2-26 x 10(-6) cm/s. In contrast, hESC-RPE and LEPI cells efficiently restricted the drug flux, and displayed even lower P-app values than those reported for bovine RPE-choroid, with the range of 0.4-32 cm(-6)/s (hESC-RPE cells) and 0.4-29 x 10(-6) cm/s, (LEPI cells). Therefore, ARPE19, ARPE19mel, and hfRPE cells failed to form a tight barrier, whereas hESC-RPE and LEPI cells restricted the drug flux to a similar extent as bovine RPE-choroid. Therefore, LEPI and hESC-RPE cells are valuable tools in ocular drug discovery.
Subject: retinal pigment epithelium
outer blood-retinal barrier
cell models
drug permeation
differentiation
tight junctions
ocular drug delivery
PIGMENT EPITHELIUM
PLASMA-MEMBRANES
MELANIN BINDING
ARPE-19 CELLS
EXPRESSION
PERMEABILITY
PREDICTION
TISSUE
317 Pharmacy
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