RETRACTED: Drug Flux across RPE Cell Models: The Hunt for an Appropriate Outer Blood–Retinal Barrier Model for Use in Early Drug Discovery
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Culture
2.2. Permeation Studies
2.3. Drug Concentration Measurements
3. Results
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Compound | 1 LogD7.4 (Predicted, ACDLabs) | Molecular Weight (g/mol) | 2 Manufacturer | Exposure Concentration (µg/mL) |
---|---|---|---|---|
Aztreonam | −4.32 | 435.4 | Fluka | 10 |
Ciprofloxacin | −0.29 | 331.3 | BioChemica | 1 |
Dexamethasone | 1.92 | 392.5 | Sigma-Aldrich | 10 |
Fluconazole | 0.45 | 306.3 | Sigma-Aldrich | 1 |
Ganciclovir | −1.61 | 255.2 | Sigma-Aldrich | 1 |
Ketorolac | −0.34 | 255.3 | Sigma-Aldrich | 1 |
Methotrexate | -5.1 | 454.4 | Fluka | 1 |
Quinidine | 1.17 | 324.4 | Sigma-Aldrich | 10 |
Voriconazole | 1.21 | 349.3 | Fluka | 10 |
Compound | LEPI | hESC-RPE (Regea08/017) | hESC-RPE (Regea08/023) | Bovine RPE-Choroid 1 |
---|---|---|---|---|
Aztreonam | 4.8 | n.a. | n.a. | 1.2 |
Ciprofloxacin | 3.9 | 1.9 | 1.1 | 6.7 |
Dexamethasone | 1.1 | n.a. | n.a. | n.d. |
Fluconazole | 1.5 | 1.1 | 1.1 | 1.2 |
Ganciclovir | 2.7 | 2.9 | 1.3 | 1.5 |
Ketorolac | 3.1 | 1.8 | 1.3 | 14.5 |
Methotrexate | 3.0 | 4.4 | 1.8 | 2.1 |
Quinidine | n.a. | 0.9 | 0.7 | n.a. |
Voriconazole | n.a. | 1.1 | 1.0 | 1.2 |
Cell Model | Culture Conditions | Tight Junction Protein Expression | Pigmentation | Barrier Properties: Conclusions of this Study | Assays in Which the Cell Model can be Utilized in Early Drug Discovery |
---|---|---|---|---|---|
Cell lines | |||||
ARPE19 | simple to demanding; variation between laboratories | yes | no | leaky | Drug uptake, active transport |
ARPE19mel | simple | yes | can be controlled; from low to heavy | leaky | Drug uptake: quantitative effects of pigmentation |
LEPI | simple | yes | no | tight | Drug uptake and permeation |
Primary RPE cells | |||||
hfRPE | simple | yes | low/modest | leaky | Drug uptake, active transport |
Stem-cell based RPE cells | |||||
hESC-RPE | demanding; long differentiation time, requires specialized conditions and expensive supplements | yes | heavy | tight | Drug uptake and permeation |
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Hellinen, L.; Hongisto, H.; Ramsay, E.; Kaarniranta, K.; Vellonen, K.-S.; Skottman, H.; Ruponen, M. RETRACTED: Drug Flux across RPE Cell Models: The Hunt for an Appropriate Outer Blood–Retinal Barrier Model for Use in Early Drug Discovery. Pharmaceutics 2020, 12, 176. https://doi.org/10.3390/pharmaceutics12020176
Hellinen L, Hongisto H, Ramsay E, Kaarniranta K, Vellonen K-S, Skottman H, Ruponen M. RETRACTED: Drug Flux across RPE Cell Models: The Hunt for an Appropriate Outer Blood–Retinal Barrier Model for Use in Early Drug Discovery. Pharmaceutics. 2020; 12(2):176. https://doi.org/10.3390/pharmaceutics12020176
Chicago/Turabian StyleHellinen, Laura, Heidi Hongisto, Eva Ramsay, Kai Kaarniranta, Kati-Sisko Vellonen, Heli Skottman, and Marika Ruponen. 2020. "RETRACTED: Drug Flux across RPE Cell Models: The Hunt for an Appropriate Outer Blood–Retinal Barrier Model for Use in Early Drug Discovery" Pharmaceutics 12, no. 2: 176. https://doi.org/10.3390/pharmaceutics12020176
APA StyleHellinen, L., Hongisto, H., Ramsay, E., Kaarniranta, K., Vellonen, K.-S., Skottman, H., & Ruponen, M. (2020). RETRACTED: Drug Flux across RPE Cell Models: The Hunt for an Appropriate Outer Blood–Retinal Barrier Model for Use in Early Drug Discovery. Pharmaceutics, 12(2), 176. https://doi.org/10.3390/pharmaceutics12020176