Partitioning and Spatial Distribution of Drugs in Ocular Surface Tissues
Abstract
:1. Introduction
2. Materials and Methods
2.1. Drug Molecules
2.2. Drug Distribution in Porcine Ocular Tissues Ex Vivo
2.2.1. Preparation of Porcine Tissues
2.2.2. Drug Distribution into the Ocular Tissues
2.2.3. Calculation of Partition Coefficients
2.3. Cell Uptake in Human Corneal Epithelial (HCE) Cells In Vitro
2.3.1. HCE Cells
2.3.2. Cell Uptake Study
2.3.3. Protein Concentration of the HCE Samples
2.3.4. Determination of Intracellular Drug Concentration
2.3.5. Calculation of Partition Coefficients from Uptake Study
2.4. Analyses of Ex Vivo and In Vitro Samples
2.4.1. Sample Preparation for LC-MS/MS
2.4.2. LC-MS/MS Analyses
2.5. Drug Distribution in Rabbit Cornea In Vivo
2.5.1. Rabbit Tissue Preparation
2.5.2. MALDI-IMS
3. Results
3.1. Drug Distribution in Porcine Ocular Tissues Ex Vivo
3.2. Apparent Distribution Coefficients in Porcine Ocular Tissues Ex Vivo
3.3. Uptake of Beta-Blocking Drugs in HCE Cells
3.4. Distribution Patterns of the Drugs in the Rabbit Cornea
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Beta-Blocking Drugs | Log D7.4 * | Molecular Weight (g/mol) | Manufacturer |
---|---|---|---|
Atenolol | −1.76 | 266.34 | Sigma-Aldrich, St. Louis, MO, USA |
Nadolol | −1.54 | 309.40 | Sigma-Aldrich, St. Louis, MO, USA |
Timolol | −1.43 | 316.42 | Sigma-Aldrich, St. Louis, MO, USA |
Pindolol | −0.5 | 248.23 | Sigma-Aldrich, St. Louis, MO, USA |
Metoprolol | 0.06 | 267.36 | Sigma-Aldrich, St. Louis, MO, USA |
Betaxolol | 0.43 | 307.43 | Alcon, Fort Worth, TX, USA |
Propranolol | 0.79 | 259.34 | Sigma-Aldrich, St. Louis, MO, USA |
Beta-Blocking Drugs | Epithelium | Stroma | ||
---|---|---|---|---|
10 min | 60 min | 10 min | 60 min | |
Pindolol | 0.21 ± 0.01 | 0.356± 0.08 | 0.57 ± 0.00 | 0.83 ± 0.13 |
Timolol | 0.19 ± 0.02 | 0.25 ± 0.08 | 0.36 ± 0.01 | 0.45 ± 0.17 |
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Balla, A.; Auriola, S.; Grey, A.C.; Demarais, N.J.; Valtari, A.; Heikkinen, E.M.; Toropainen, E.; Urtti, A.; Vellonen, K.-S.; Ruponen, M. Partitioning and Spatial Distribution of Drugs in Ocular Surface Tissues. Pharmaceutics 2021, 13, 658. https://doi.org/10.3390/pharmaceutics13050658
Balla A, Auriola S, Grey AC, Demarais NJ, Valtari A, Heikkinen EM, Toropainen E, Urtti A, Vellonen K-S, Ruponen M. Partitioning and Spatial Distribution of Drugs in Ocular Surface Tissues. Pharmaceutics. 2021; 13(5):658. https://doi.org/10.3390/pharmaceutics13050658
Chicago/Turabian StyleBalla, Anusha, Seppo Auriola, Angus C. Grey, Nicholas J. Demarais, Annika Valtari, Emma M. Heikkinen, Elisa Toropainen, Arto Urtti, Kati-Sisko Vellonen, and Marika Ruponen. 2021. "Partitioning and Spatial Distribution of Drugs in Ocular Surface Tissues" Pharmaceutics 13, no. 5: 658. https://doi.org/10.3390/pharmaceutics13050658
APA StyleBalla, A., Auriola, S., Grey, A. C., Demarais, N. J., Valtari, A., Heikkinen, E. M., Toropainen, E., Urtti, A., Vellonen, K.-S., & Ruponen, M. (2021). Partitioning and Spatial Distribution of Drugs in Ocular Surface Tissues. Pharmaceutics, 13(5), 658. https://doi.org/10.3390/pharmaceutics13050658