A versatile, compartmentalised gut-on-a-chip system for pharmacological and toxicological analyses

Abstract A novel, integrated, in vitro gastrointestinal (GI) system is presented to study oral bioavailability parameters of small molecules. Three compartments were combined into one hyphenated, flow-through set-up. In the first compartment, a compound was exposed dynamically to enzymatic digestion...

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Autores principales:	Pim de Haan, Milou J. C. Santbergen, Meike van der Zande, Hans Bouwmeester, Michel W. F. Nielen, Elisabeth Verpoorte
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/aa2e8b405d444088bfbbdecd824d68f2
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spelling	oai:doaj.org-article:aa2e8b405d444088bfbbdecd824d68f22021-12-02T13:30:52ZA versatile, compartmentalised gut-on-a-chip system for pharmacological and toxicological analyses10.1038/s41598-021-84187-92045-2322https://doaj.org/article/aa2e8b405d444088bfbbdecd824d68f22021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84187-9https://doaj.org/toc/2045-2322Abstract A novel, integrated, in vitro gastrointestinal (GI) system is presented to study oral bioavailability parameters of small molecules. Three compartments were combined into one hyphenated, flow-through set-up. In the first compartment, a compound was exposed dynamically to enzymatic digestion in three consecutive microreactors, mimicking the processes of the mouth, stomach, and intestine. The resulting solution (chyme) continued to the second compartment, a flow-through barrier model of the intestinal epithelium allowing absorption of the compound and metabolites thereof. The composition of the effluents from the barrier model were analysed either offline by electrospray-ionisation-mass spectrometry (ESI–MS), or online in the final compartment using chip-based ESI–MS. Two model drugs, omeprazole and verapamil, were used to test the integrated model. Omeprazole was shown to be broken down upon treatment with gastric acid, but reached the cell barrier unharmed when introduced to the system in a manner emulating an enteric-coated formulation. In contrast, verapamil was unaffected by digestion. Finally, a reduced uptake of verapamil was observed when verapamil was introduced to the system dissolved in apple juice, a simple food matrix. It is envisaged that this integrated, compartmentalised GI system has potential for enabling future research in the fields of pharmacology, toxicology, and nutrition.Pim de HaanMilou J. C. SantbergenMeike van der ZandeHans BouwmeesterMichel W. F. NielenElisabeth VerpoorteNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Pim de Haan Milou J. C. Santbergen Meike van der Zande Hans Bouwmeester Michel W. F. Nielen Elisabeth Verpoorte A versatile, compartmentalised gut-on-a-chip system for pharmacological and toxicological analyses
description	Abstract A novel, integrated, in vitro gastrointestinal (GI) system is presented to study oral bioavailability parameters of small molecules. Three compartments were combined into one hyphenated, flow-through set-up. In the first compartment, a compound was exposed dynamically to enzymatic digestion in three consecutive microreactors, mimicking the processes of the mouth, stomach, and intestine. The resulting solution (chyme) continued to the second compartment, a flow-through barrier model of the intestinal epithelium allowing absorption of the compound and metabolites thereof. The composition of the effluents from the barrier model were analysed either offline by electrospray-ionisation-mass spectrometry (ESI–MS), or online in the final compartment using chip-based ESI–MS. Two model drugs, omeprazole and verapamil, were used to test the integrated model. Omeprazole was shown to be broken down upon treatment with gastric acid, but reached the cell barrier unharmed when introduced to the system in a manner emulating an enteric-coated formulation. In contrast, verapamil was unaffected by digestion. Finally, a reduced uptake of verapamil was observed when verapamil was introduced to the system dissolved in apple juice, a simple food matrix. It is envisaged that this integrated, compartmentalised GI system has potential for enabling future research in the fields of pharmacology, toxicology, and nutrition.
format	article
author	Pim de Haan Milou J. C. Santbergen Meike van der Zande Hans Bouwmeester Michel W. F. Nielen Elisabeth Verpoorte
author_facet	Pim de Haan Milou J. C. Santbergen Meike van der Zande Hans Bouwmeester Michel W. F. Nielen Elisabeth Verpoorte
author_sort	Pim de Haan
title	A versatile, compartmentalised gut-on-a-chip system for pharmacological and toxicological analyses
title_short	A versatile, compartmentalised gut-on-a-chip system for pharmacological and toxicological analyses
title_full	A versatile, compartmentalised gut-on-a-chip system for pharmacological and toxicological analyses
title_fullStr	A versatile, compartmentalised gut-on-a-chip system for pharmacological and toxicological analyses
title_full_unstemmed	A versatile, compartmentalised gut-on-a-chip system for pharmacological and toxicological analyses
title_sort	versatile, compartmentalised gut-on-a-chip system for pharmacological and toxicological analyses
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/aa2e8b405d444088bfbbdecd824d68f2
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A versatile, compartmentalised gut-on-a-chip system for pharmacological and toxicological analyses

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