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In Vitro–In Silico Modeling of Caffeine and Diclofenac Permeation in Static and Fluidic Systems with a 16HBE Lung Cell Barrier

Static in vitro permeation experiments are commonly used to gain insights into the permeation properties of drug substances but exhibit limitations due to missing physiologic cell stimuli. Thus, fluidic systems integrating stimuli, such as physicochemical fluxes, have been developed. However, as flu...

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Autores principales: Kovar, Lukas, Wien, Lena, Selzer, Dominik, Kohl, Yvonne, Bals, Robert, Lehr, Thorsten
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8876625/
https://www.ncbi.nlm.nih.gov/pubmed/35215362
http://dx.doi.org/10.3390/ph15020250
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author Kovar, Lukas
Wien, Lena
Selzer, Dominik
Kohl, Yvonne
Bals, Robert
Lehr, Thorsten
author_facet Kovar, Lukas
Wien, Lena
Selzer, Dominik
Kohl, Yvonne
Bals, Robert
Lehr, Thorsten
author_sort Kovar, Lukas
collection PubMed
description Static in vitro permeation experiments are commonly used to gain insights into the permeation properties of drug substances but exhibit limitations due to missing physiologic cell stimuli. Thus, fluidic systems integrating stimuli, such as physicochemical fluxes, have been developed. However, as fluidic in vitro studies display higher complexity compared to static systems, analysis of experimental readouts is challenging. Here, the integration of in silico tools holds the potential to evaluate fluidic experiments and to investigate specific simulation scenarios. This study aimed to develop in silico models that describe and predict the permeation and disposition of two model substances in a static and fluidic in vitro system. For this, in vitro permeation studies with a 16HBE cellular barrier under both static and fluidic conditions were performed over 72 h. In silico models were implemented and employed to describe and predict concentration–time profiles of caffeine and diclofenac in various experimental setups. For both substances, in silico modeling identified reduced apparent permeabilities in the fluidic compared to the static cellular setting. The developed in vitro–in silico modeling framework can be expanded further, integrating additional cell tissues in the fluidic system, and can be employed in future studies to model pharmacokinetic and pharmacodynamic drug behavior.
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spelling pubmed-88766252022-02-26 In Vitro–In Silico Modeling of Caffeine and Diclofenac Permeation in Static and Fluidic Systems with a 16HBE Lung Cell Barrier Kovar, Lukas Wien, Lena Selzer, Dominik Kohl, Yvonne Bals, Robert Lehr, Thorsten Pharmaceuticals (Basel) Article Static in vitro permeation experiments are commonly used to gain insights into the permeation properties of drug substances but exhibit limitations due to missing physiologic cell stimuli. Thus, fluidic systems integrating stimuli, such as physicochemical fluxes, have been developed. However, as fluidic in vitro studies display higher complexity compared to static systems, analysis of experimental readouts is challenging. Here, the integration of in silico tools holds the potential to evaluate fluidic experiments and to investigate specific simulation scenarios. This study aimed to develop in silico models that describe and predict the permeation and disposition of two model substances in a static and fluidic in vitro system. For this, in vitro permeation studies with a 16HBE cellular barrier under both static and fluidic conditions were performed over 72 h. In silico models were implemented and employed to describe and predict concentration–time profiles of caffeine and diclofenac in various experimental setups. For both substances, in silico modeling identified reduced apparent permeabilities in the fluidic compared to the static cellular setting. The developed in vitro–in silico modeling framework can be expanded further, integrating additional cell tissues in the fluidic system, and can be employed in future studies to model pharmacokinetic and pharmacodynamic drug behavior. MDPI 2022-02-18 /pmc/articles/PMC8876625/ /pubmed/35215362 http://dx.doi.org/10.3390/ph15020250 Text en © 2022 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
Kovar, Lukas
Wien, Lena
Selzer, Dominik
Kohl, Yvonne
Bals, Robert
Lehr, Thorsten
In Vitro–In Silico Modeling of Caffeine and Diclofenac Permeation in Static and Fluidic Systems with a 16HBE Lung Cell Barrier
title In Vitro–In Silico Modeling of Caffeine and Diclofenac Permeation in Static and Fluidic Systems with a 16HBE Lung Cell Barrier
title_full In Vitro–In Silico Modeling of Caffeine and Diclofenac Permeation in Static and Fluidic Systems with a 16HBE Lung Cell Barrier
title_fullStr In Vitro–In Silico Modeling of Caffeine and Diclofenac Permeation in Static and Fluidic Systems with a 16HBE Lung Cell Barrier
title_full_unstemmed In Vitro–In Silico Modeling of Caffeine and Diclofenac Permeation in Static and Fluidic Systems with a 16HBE Lung Cell Barrier
title_short In Vitro–In Silico Modeling of Caffeine and Diclofenac Permeation in Static and Fluidic Systems with a 16HBE Lung Cell Barrier
title_sort in vitro–in silico modeling of caffeine and diclofenac permeation in static and fluidic systems with a 16hbe lung cell barrier
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8876625/
https://www.ncbi.nlm.nih.gov/pubmed/35215362
http://dx.doi.org/10.3390/ph15020250
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