The Path from Nasal Tissue to Nasal Mucosa on Chip: Part 2—Advanced Microfluidic Nasal In Vitro Model for Drug Absorption Testing
The nasal mucosa, being accessible and highly vascularized, opens up new opportunities for the systemic administration of drugs. However, there are several protective functions like the mucociliary clearance, a physiological barrier which represents is a difficult obstacle for drug candidates to ove...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-10-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/10/2439 |
| _version_ | 1797572579978903552 |
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| author | Eugen Viktor Koch Sebastian Bendas Kristina Nehlsen Tobias May Stephan Reichl Andreas Dietzel |
| author_facet | Eugen Viktor Koch Sebastian Bendas Kristina Nehlsen Tobias May Stephan Reichl Andreas Dietzel |
| author_sort | Eugen Viktor Koch |
| collection | DOAJ |
| description | The nasal mucosa, being accessible and highly vascularized, opens up new opportunities for the systemic administration of drugs. However, there are several protective functions like the mucociliary clearance, a physiological barrier which represents is a difficult obstacle for drug candidates to overcome. For this reason, effective testing procedures are required in the preclinical phase of pharmaceutical development. Based on a recently reported immortalized porcine nasal epithelial cell line, we developed a test platform based on a tissue-compatible microfluidic chip. In this study, a biomimetic glass chip, which was equipped with a controlled bidirectional airflow to induce a physiologically relevant wall shear stress on the epithelial cell layer, was microfabricated. By developing a membrane transfer technique, the epithelial cell layer could be pre-cultivated in a static holder prior to cultivation in a microfluidic environment. The dynamic cultivation within the chip showed a homogenous distribution of the mucus film on top of the cell layer and a significant increase in cilia formation compared to the static cultivation condition. In addition, the recording of the ciliary transport mechanism by microparticle image velocimetry was successful. Using FITC-dextran 4000 as an example, it was shown that this nasal mucosa on a chip is suitable for permeation studies. The obtained permeation coefficient was in the range of values determined by means of other established in vitro and in vivo models. This novel nasal mucosa on chip could, in future, be automated and used as a substitute for animal testing. |
| first_indexed | 2024-03-10T20:58:54Z |
| format | Article |
| id | doaj.art-9bcd82d78acc4ff0b37d5c4ba74b7725 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T20:58:54Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-9bcd82d78acc4ff0b37d5c4ba74b77252023-11-19T17:44:32ZengMDPI AGPharmaceutics1999-49232023-10-011510243910.3390/pharmaceutics15102439The Path from Nasal Tissue to Nasal Mucosa on Chip: Part 2—Advanced Microfluidic Nasal In Vitro Model for Drug Absorption TestingEugen Viktor Koch0Sebastian Bendas1Kristina Nehlsen2Tobias May3Stephan Reichl4Andreas Dietzel5Institute of Microtechnology, TU Braunschweig, Alte Salzdahlumer Str. 203, 38124 Braunschweig, GermanyCenter of Pharmaceutical Engineering, Franz-Liszt Str. 35 a, 38106 Braunschweig, GermanyInSCREENeX GmbH, Inhoffenstr. 7, 38124 Braunschweig, GermanyInSCREENeX GmbH, Inhoffenstr. 7, 38124 Braunschweig, GermanyCenter of Pharmaceutical Engineering, Franz-Liszt Str. 35 a, 38106 Braunschweig, GermanyInstitute of Microtechnology, TU Braunschweig, Alte Salzdahlumer Str. 203, 38124 Braunschweig, GermanyThe nasal mucosa, being accessible and highly vascularized, opens up new opportunities for the systemic administration of drugs. However, there are several protective functions like the mucociliary clearance, a physiological barrier which represents is a difficult obstacle for drug candidates to overcome. For this reason, effective testing procedures are required in the preclinical phase of pharmaceutical development. Based on a recently reported immortalized porcine nasal epithelial cell line, we developed a test platform based on a tissue-compatible microfluidic chip. In this study, a biomimetic glass chip, which was equipped with a controlled bidirectional airflow to induce a physiologically relevant wall shear stress on the epithelial cell layer, was microfabricated. By developing a membrane transfer technique, the epithelial cell layer could be pre-cultivated in a static holder prior to cultivation in a microfluidic environment. The dynamic cultivation within the chip showed a homogenous distribution of the mucus film on top of the cell layer and a significant increase in cilia formation compared to the static cultivation condition. In addition, the recording of the ciliary transport mechanism by microparticle image velocimetry was successful. Using FITC-dextran 4000 as an example, it was shown that this nasal mucosa on a chip is suitable for permeation studies. The obtained permeation coefficient was in the range of values determined by means of other established in vitro and in vivo models. This novel nasal mucosa on chip could, in future, be automated and used as a substitute for animal testing.https://www.mdpi.com/1999-4923/15/10/2439organ on chipmicrofluidicsnasal mucosanasal drug administrationpermeation testmucociliary clearance |
| spellingShingle | Eugen Viktor Koch Sebastian Bendas Kristina Nehlsen Tobias May Stephan Reichl Andreas Dietzel The Path from Nasal Tissue to Nasal Mucosa on Chip: Part 2—Advanced Microfluidic Nasal In Vitro Model for Drug Absorption Testing Pharmaceutics organ on chip microfluidics nasal mucosa nasal drug administration permeation test mucociliary clearance |
| title | The Path from Nasal Tissue to Nasal Mucosa on Chip: Part 2—Advanced Microfluidic Nasal In Vitro Model for Drug Absorption Testing |
| title_full | The Path from Nasal Tissue to Nasal Mucosa on Chip: Part 2—Advanced Microfluidic Nasal In Vitro Model for Drug Absorption Testing |
| title_fullStr | The Path from Nasal Tissue to Nasal Mucosa on Chip: Part 2—Advanced Microfluidic Nasal In Vitro Model for Drug Absorption Testing |
| title_full_unstemmed | The Path from Nasal Tissue to Nasal Mucosa on Chip: Part 2—Advanced Microfluidic Nasal In Vitro Model for Drug Absorption Testing |
| title_short | The Path from Nasal Tissue to Nasal Mucosa on Chip: Part 2—Advanced Microfluidic Nasal In Vitro Model for Drug Absorption Testing |
| title_sort | path from nasal tissue to nasal mucosa on chip part 2 advanced microfluidic nasal in vitro model for drug absorption testing |
| topic | organ on chip microfluidics nasal mucosa nasal drug administration permeation test mucociliary clearance |
| url | https://www.mdpi.com/1999-4923/15/10/2439 |
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