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Dynamic Ex Vivo Porcine Eye Model to Measure Ophthalmic Drug Penetration under Simulated Lacrimal Flow
Animal models are still used in the research and development of ophthalmic drug products, mainly due to the difficulty in simulating natural physiological conditions with in vitro models, as there is a lack of dynamic protection mechanisms. Therefore, developing alternative ophthalmic models that ev...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10534681/ https://www.ncbi.nlm.nih.gov/pubmed/37765293 http://dx.doi.org/10.3390/pharmaceutics15092325 |
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author | Barbalho, Geisa N. Falcão, Manuel A. Lopes, Jefferson M. S. Lopes, Júlia M. Contarato, Jonad L. A. Gelfuso, Guilherme M. Cunha-Filho, Marcilio Gratieri, Tais |
author_facet | Barbalho, Geisa N. Falcão, Manuel A. Lopes, Jefferson M. S. Lopes, Júlia M. Contarato, Jonad L. A. Gelfuso, Guilherme M. Cunha-Filho, Marcilio Gratieri, Tais |
author_sort | Barbalho, Geisa N. |
collection | PubMed |
description | Animal models are still used in the research and development of ophthalmic drug products, mainly due to the difficulty in simulating natural physiological conditions with in vitro models, as there is a lack of dynamic protection mechanisms. Therefore, developing alternative ophthalmic models that evaluate drug penetration in the cornea while applying dynamic protection barriers is a contemporary challenge. This study aimed to develop a dynamic ex vivo model using porcine eyes with a simulated lacrimal flow to evaluate the performance of pharmaceutical drug products. A glass donor cell to support a simulated tear flow was designed, optimized, and custom-made. The system was challenged with different formulations (with fluconazole) including excipients with different viscosities (poloxamer 407) and mucoadhesive properties (chitosan). The results were compared to those obtained from a conventional excised cornea model mounted in Franz-type diffusion cells. The dynamic model could differentiate formulations, while the static model did not, overestimating ex vivo drug penetrated amounts. Hence, the dynamic model with simulated tear flow showed to be a simple and promising new alternative method for the drug penetration of ophthalmic formulations that ultimately can reduce the number of animals used in research. |
format | Online Article Text |
id | pubmed-10534681 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-105346812023-09-29 Dynamic Ex Vivo Porcine Eye Model to Measure Ophthalmic Drug Penetration under Simulated Lacrimal Flow Barbalho, Geisa N. Falcão, Manuel A. Lopes, Jefferson M. S. Lopes, Júlia M. Contarato, Jonad L. A. Gelfuso, Guilherme M. Cunha-Filho, Marcilio Gratieri, Tais Pharmaceutics Article Animal models are still used in the research and development of ophthalmic drug products, mainly due to the difficulty in simulating natural physiological conditions with in vitro models, as there is a lack of dynamic protection mechanisms. Therefore, developing alternative ophthalmic models that evaluate drug penetration in the cornea while applying dynamic protection barriers is a contemporary challenge. This study aimed to develop a dynamic ex vivo model using porcine eyes with a simulated lacrimal flow to evaluate the performance of pharmaceutical drug products. A glass donor cell to support a simulated tear flow was designed, optimized, and custom-made. The system was challenged with different formulations (with fluconazole) including excipients with different viscosities (poloxamer 407) and mucoadhesive properties (chitosan). The results were compared to those obtained from a conventional excised cornea model mounted in Franz-type diffusion cells. The dynamic model could differentiate formulations, while the static model did not, overestimating ex vivo drug penetrated amounts. Hence, the dynamic model with simulated tear flow showed to be a simple and promising new alternative method for the drug penetration of ophthalmic formulations that ultimately can reduce the number of animals used in research. MDPI 2023-09-15 /pmc/articles/PMC10534681/ /pubmed/37765293 http://dx.doi.org/10.3390/pharmaceutics15092325 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Barbalho, Geisa N. Falcão, Manuel A. Lopes, Jefferson M. S. Lopes, Júlia M. Contarato, Jonad L. A. Gelfuso, Guilherme M. Cunha-Filho, Marcilio Gratieri, Tais Dynamic Ex Vivo Porcine Eye Model to Measure Ophthalmic Drug Penetration under Simulated Lacrimal Flow |
title | Dynamic Ex Vivo Porcine Eye Model to Measure Ophthalmic Drug Penetration under Simulated Lacrimal Flow |
title_full | Dynamic Ex Vivo Porcine Eye Model to Measure Ophthalmic Drug Penetration under Simulated Lacrimal Flow |
title_fullStr | Dynamic Ex Vivo Porcine Eye Model to Measure Ophthalmic Drug Penetration under Simulated Lacrimal Flow |
title_full_unstemmed | Dynamic Ex Vivo Porcine Eye Model to Measure Ophthalmic Drug Penetration under Simulated Lacrimal Flow |
title_short | Dynamic Ex Vivo Porcine Eye Model to Measure Ophthalmic Drug Penetration under Simulated Lacrimal Flow |
title_sort | dynamic ex vivo porcine eye model to measure ophthalmic drug penetration under simulated lacrimal flow |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10534681/ https://www.ncbi.nlm.nih.gov/pubmed/37765293 http://dx.doi.org/10.3390/pharmaceutics15092325 |
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