Drug Flux Across RPE Cell Models: The Hunt for An Appropriate Outer Blood–Retinal Barrier Model for Use in Early Drug Discovery
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 permeabili...
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| Format: | Article |
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MDPI AG
2020-02-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/12/2/176 |
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| author | Laura Hellinen Heidi Hongisto Eva Ramsay Kai Kaarniranta Kati-Sisko Vellonen Heli Skottman Marika Ruponen |
| author_facet | Laura Hellinen Heidi Hongisto Eva Ramsay Kai Kaarniranta Kati-Sisko Vellonen Heli Skottman Marika Ruponen |
| author_sort | Laura Hellinen |
| collection | DOAJ |
| description | 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<sub>app</sub> value range, with relatively high permeation rates (5.2−26 × 10<sup>−6</sup> cm/s. In contrast, hESC-RPE and LEPI cells efficiently restricted the drug flux, and displayed even lower P<sub>app</sub> values than those reported for bovine RPE-choroid, with the range of 0.4−32 cm<sup>−6</sup>/s (hESC-RPE cells) and 0.4−29 × 10<sup>−6</sup> 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. |
| first_indexed | 2024-04-11T13:43:09Z |
| format | Article |
| id | doaj.art-8ee02da0d3944372a3092b7c49eff940 |
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| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-11T13:43:09Z |
| publishDate | 2020-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-8ee02da0d3944372a3092b7c49eff9402022-12-22T04:21:10ZengMDPI AGPharmaceutics1999-49232020-02-0112217610.3390/pharmaceutics12020176pharmaceutics12020176Drug Flux Across RPE Cell Models: The Hunt for An Appropriate Outer Blood–Retinal Barrier Model for Use in Early Drug DiscoveryLaura Hellinen0Heidi Hongisto1Eva Ramsay2Kai Kaarniranta3Kati-Sisko Vellonen4Heli Skottman5Marika Ruponen6School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, 70210 Kuopio, FinlandDepartment of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, 70210 Kuopio, FinlandDrug Research Programme, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, FI-00014 Helsinki, FinlandDepartment of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, 70210 Kuopio, FinlandSchool of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, 70210 Kuopio, FinlandFaculty of Medicine and Health Technology, BioMediTech, Tampere University, 33520 Tampere, FinlandSchool of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, 70210 Kuopio, FinlandThe 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<sub>app</sub> value range, with relatively high permeation rates (5.2−26 × 10<sup>−6</sup> cm/s. In contrast, hESC-RPE and LEPI cells efficiently restricted the drug flux, and displayed even lower P<sub>app</sub> values than those reported for bovine RPE-choroid, with the range of 0.4−32 cm<sup>−6</sup>/s (hESC-RPE cells) and 0.4−29 × 10<sup>−6</sup> 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.https://www.mdpi.com/1999-4923/12/2/176retinal pigment epitheliumouter blood–retinal barriercell modelsdrug permeationdifferentiationtight junctionsocular drug delivery |
| spellingShingle | Laura Hellinen Heidi Hongisto Eva Ramsay Kai Kaarniranta Kati-Sisko Vellonen Heli Skottman Marika Ruponen Drug Flux Across RPE Cell Models: The Hunt for An Appropriate Outer Blood–Retinal Barrier Model for Use in Early Drug Discovery Pharmaceutics retinal pigment epithelium outer blood–retinal barrier cell models drug permeation differentiation tight junctions ocular drug delivery |
| title | Drug Flux Across RPE Cell Models: The Hunt for An Appropriate Outer Blood–Retinal Barrier Model for Use in Early Drug Discovery |
| title_full | Drug Flux Across RPE Cell Models: The Hunt for An Appropriate Outer Blood–Retinal Barrier Model for Use in Early Drug Discovery |
| title_fullStr | Drug Flux Across RPE Cell Models: The Hunt for An Appropriate Outer Blood–Retinal Barrier Model for Use in Early Drug Discovery |
| title_full_unstemmed | Drug Flux Across RPE Cell Models: The Hunt for An Appropriate Outer Blood–Retinal Barrier Model for Use in Early Drug Discovery |
| title_short | Drug Flux Across RPE Cell Models: The Hunt for An Appropriate Outer Blood–Retinal Barrier Model for Use in Early Drug Discovery |
| title_sort | drug flux across rpe cell models the hunt for an appropriate outer blood retinal barrier model for use in early drug discovery |
| topic | retinal pigment epithelium outer blood–retinal barrier cell models drug permeation differentiation tight junctions ocular drug delivery |
| url | https://www.mdpi.com/1999-4923/12/2/176 |
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