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Microfluidic System for In Vivo-Like Drug Permeation Studies with Dynamic Dilution Profiles

Automated biomimetic systems for the preclinical testing of drugs are of great interest. Here, an in vitro testing platform for in vivo adapted drug absorption studies is presented. It has been designed with a focus on easy handling and the usability of established cell cultivation techniques in sta...

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Detalles Bibliográficos
Autores principales: Lorenz, Thomas, Kirschke, Mona, Ledwig, Verena, Reichl, Stephan, Dietzel, Andreas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147988/
https://www.ncbi.nlm.nih.gov/pubmed/34063027
http://dx.doi.org/10.3390/bioengineering8050058
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author Lorenz, Thomas
Kirschke, Mona
Ledwig, Verena
Reichl, Stephan
Dietzel, Andreas
author_facet Lorenz, Thomas
Kirschke, Mona
Ledwig, Verena
Reichl, Stephan
Dietzel, Andreas
author_sort Lorenz, Thomas
collection PubMed
description Automated biomimetic systems for the preclinical testing of drugs are of great interest. Here, an in vitro testing platform for in vivo adapted drug absorption studies is presented. It has been designed with a focus on easy handling and the usability of established cell cultivation techniques in standard well plate inserts. The platform consists of a microfluidic device, which accommodates a well plate insert with pre-cultivated cells, and provides a fluid flow with dynamic drug dilution profiles. A low-cost single-board computer with a touchscreen was used as a control unit. This provides a graphical user interface, controls the syringe pump flow rates, and records the transepithelial electrical resistance. It thereby enables automated parallel testing in multiple devices at the same time. To demonstrate functionality, an MDCK cell layer was used as a model for an epithelial barrier for drug permeation testing. This confirms the possibility of performing absorption studies on barrier tissues under conditions close to those in vivo. Therefore, a further reduction in animal experiments can be expected.
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spelling pubmed-81479882021-05-26 Microfluidic System for In Vivo-Like Drug Permeation Studies with Dynamic Dilution Profiles Lorenz, Thomas Kirschke, Mona Ledwig, Verena Reichl, Stephan Dietzel, Andreas Bioengineering (Basel) Article Automated biomimetic systems for the preclinical testing of drugs are of great interest. Here, an in vitro testing platform for in vivo adapted drug absorption studies is presented. It has been designed with a focus on easy handling and the usability of established cell cultivation techniques in standard well plate inserts. The platform consists of a microfluidic device, which accommodates a well plate insert with pre-cultivated cells, and provides a fluid flow with dynamic drug dilution profiles. A low-cost single-board computer with a touchscreen was used as a control unit. This provides a graphical user interface, controls the syringe pump flow rates, and records the transepithelial electrical resistance. It thereby enables automated parallel testing in multiple devices at the same time. To demonstrate functionality, an MDCK cell layer was used as a model for an epithelial barrier for drug permeation testing. This confirms the possibility of performing absorption studies on barrier tissues under conditions close to those in vivo. Therefore, a further reduction in animal experiments can be expected. MDPI 2021-05-05 /pmc/articles/PMC8147988/ /pubmed/34063027 http://dx.doi.org/10.3390/bioengineering8050058 Text en © 2021 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
Lorenz, Thomas
Kirschke, Mona
Ledwig, Verena
Reichl, Stephan
Dietzel, Andreas
Microfluidic System for In Vivo-Like Drug Permeation Studies with Dynamic Dilution Profiles
title Microfluidic System for In Vivo-Like Drug Permeation Studies with Dynamic Dilution Profiles
title_full Microfluidic System for In Vivo-Like Drug Permeation Studies with Dynamic Dilution Profiles
title_fullStr Microfluidic System for In Vivo-Like Drug Permeation Studies with Dynamic Dilution Profiles
title_full_unstemmed Microfluidic System for In Vivo-Like Drug Permeation Studies with Dynamic Dilution Profiles
title_short Microfluidic System for In Vivo-Like Drug Permeation Studies with Dynamic Dilution Profiles
title_sort microfluidic system for in vivo-like drug permeation studies with dynamic dilution profiles
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147988/
https://www.ncbi.nlm.nih.gov/pubmed/34063027
http://dx.doi.org/10.3390/bioengineering8050058
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