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The Path from Nasal Tissue to Nasal Mucosa on Chip: Part 1—Establishing a Nasal In Vitro Model for Drug Delivery Testing Based on a Novel Cell Line

In recent years, there has been a significant increase in the registration of drugs for nasal application with systemic effects. Previous preclinical in vitro test systems for transmucosal drug absorption studies have mostly been based on primary cells or on tumor cell lines such as RPMI 2650, but b...

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Autores principales: Bendas, Sebastian, Koch, Eugen Viktor, Nehlsen, Kristina, May, Tobias, Dietzel, Andreas, Reichl, Stephan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10536430/
https://www.ncbi.nlm.nih.gov/pubmed/37765214
http://dx.doi.org/10.3390/pharmaceutics15092245
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author Bendas, Sebastian
Koch, Eugen Viktor
Nehlsen, Kristina
May, Tobias
Dietzel, Andreas
Reichl, Stephan
author_facet Bendas, Sebastian
Koch, Eugen Viktor
Nehlsen, Kristina
May, Tobias
Dietzel, Andreas
Reichl, Stephan
author_sort Bendas, Sebastian
collection PubMed
description In recent years, there has been a significant increase in the registration of drugs for nasal application with systemic effects. Previous preclinical in vitro test systems for transmucosal drug absorption studies have mostly been based on primary cells or on tumor cell lines such as RPMI 2650, but both approaches have disadvantages. Therefore, the aim of this study was to establish and characterize a novel immortalized nasal epithelial cell line as the basis for an improved 3D cell culture model of the nasal mucosa. First, porcine primary cells were isolated and transfected. The P1 cell line obtained from this process was characterized in terms of its expression of tissue-specific properties, namely, mucus expression, cilia formation, and epithelial barrier formation. Using air–liquid interface cultivation, it was possible to achieve both high mucus formation and the development of functional cilia. Epithelial integrity was expressed as both transepithelial electrical resistance and mucosal permeability, which was determined for sodium fluorescein, rhodamine B, and FITC-dextran 4000. We noted a high comparability of the novel cell culture model with native excised nasal mucosa in terms of these measures. Thus, this novel cell line seems to offer a promising approach for developing 3D nasal mucosa tissues that exhibit favorable characteristics to be used as an in vitro system for testing drug delivery systems.
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spelling pubmed-105364302023-09-29 The Path from Nasal Tissue to Nasal Mucosa on Chip: Part 1—Establishing a Nasal In Vitro Model for Drug Delivery Testing Based on a Novel Cell Line Bendas, Sebastian Koch, Eugen Viktor Nehlsen, Kristina May, Tobias Dietzel, Andreas Reichl, Stephan Pharmaceutics Article In recent years, there has been a significant increase in the registration of drugs for nasal application with systemic effects. Previous preclinical in vitro test systems for transmucosal drug absorption studies have mostly been based on primary cells or on tumor cell lines such as RPMI 2650, but both approaches have disadvantages. Therefore, the aim of this study was to establish and characterize a novel immortalized nasal epithelial cell line as the basis for an improved 3D cell culture model of the nasal mucosa. First, porcine primary cells were isolated and transfected. The P1 cell line obtained from this process was characterized in terms of its expression of tissue-specific properties, namely, mucus expression, cilia formation, and epithelial barrier formation. Using air–liquid interface cultivation, it was possible to achieve both high mucus formation and the development of functional cilia. Epithelial integrity was expressed as both transepithelial electrical resistance and mucosal permeability, which was determined for sodium fluorescein, rhodamine B, and FITC-dextran 4000. We noted a high comparability of the novel cell culture model with native excised nasal mucosa in terms of these measures. Thus, this novel cell line seems to offer a promising approach for developing 3D nasal mucosa tissues that exhibit favorable characteristics to be used as an in vitro system for testing drug delivery systems. MDPI 2023-08-30 /pmc/articles/PMC10536430/ /pubmed/37765214 http://dx.doi.org/10.3390/pharmaceutics15092245 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
Bendas, Sebastian
Koch, Eugen Viktor
Nehlsen, Kristina
May, Tobias
Dietzel, Andreas
Reichl, Stephan
The Path from Nasal Tissue to Nasal Mucosa on Chip: Part 1—Establishing a Nasal In Vitro Model for Drug Delivery Testing Based on a Novel Cell Line
title The Path from Nasal Tissue to Nasal Mucosa on Chip: Part 1—Establishing a Nasal In Vitro Model for Drug Delivery Testing Based on a Novel Cell Line
title_full The Path from Nasal Tissue to Nasal Mucosa on Chip: Part 1—Establishing a Nasal In Vitro Model for Drug Delivery Testing Based on a Novel Cell Line
title_fullStr The Path from Nasal Tissue to Nasal Mucosa on Chip: Part 1—Establishing a Nasal In Vitro Model for Drug Delivery Testing Based on a Novel Cell Line
title_full_unstemmed The Path from Nasal Tissue to Nasal Mucosa on Chip: Part 1—Establishing a Nasal In Vitro Model for Drug Delivery Testing Based on a Novel Cell Line
title_short The Path from Nasal Tissue to Nasal Mucosa on Chip: Part 1—Establishing a Nasal In Vitro Model for Drug Delivery Testing Based on a Novel Cell Line
title_sort path from nasal tissue to nasal mucosa on chip: part 1—establishing a nasal in vitro model for drug delivery testing based on a novel cell line
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10536430/
https://www.ncbi.nlm.nih.gov/pubmed/37765214
http://dx.doi.org/10.3390/pharmaceutics15092245
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