Mass Spectrometry Imaging proves differential absorption profiles of well-characterised permeability markers along the crypt-villus axis

Abstract Knowledge about the region-specific absorption profiles from the gastrointestinal tract of orally administered drugs is a critical factor guiding dosage form selection in drug development. We have used a novel approach to study three well-characterized permeability and absorption marker dru...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Anna Nilsson, Alexandra Peric, Marie Strimfors, Richard J. A. Goodwin, Martin A. Hayes, Per E. Andrén, Constanze Hilgendorf
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/45e76ae7ec17443ea148df3403eb0c61
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:45e76ae7ec17443ea148df3403eb0c61
record_format	dspace
spelling	oai:doaj.org-article:45e76ae7ec17443ea148df3403eb0c612021-12-02T15:06:14ZMass Spectrometry Imaging proves differential absorption profiles of well-characterised permeability markers along the crypt-villus axis10.1038/s41598-017-06583-42045-2322https://doaj.org/article/45e76ae7ec17443ea148df3403eb0c612017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06583-4https://doaj.org/toc/2045-2322Abstract Knowledge about the region-specific absorption profiles from the gastrointestinal tract of orally administered drugs is a critical factor guiding dosage form selection in drug development. We have used a novel approach to study three well-characterized permeability and absorption marker drugs in the intestine. Propranolol and metoprolol (highly permeable compounds) and atenolol (low-moderate permeability compound) were orally co-administered to rats. The site of drug absorption was revealed by high spatial resolution matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) and complemented by quantitative measurement of drug concentration in tissue homogenates. MALDI-MSI identified endogenous molecular markers that illustrated the villi structures and confirmed the different absorption sites assigned to histological landmarks for the three drugs. Propranolol and metoprolol showed a rapid absorption and shorter transit distance in contrast to atenolol, which was absorbed more slowly from more distal sites. This study provides novel insights into site specific absorption for each of the compounds along the crypt-villus axis, as well as confirming a proximal-distal absorption gradient along the intestine. The combined analytical approach allowed the quantification and spatial resolution of drug distribution in the intestine and provided experimental evidence for the suggested absorption behaviour of low and highly permeable compounds.Anna NilssonAlexandra PericMarie StrimforsRichard J. A. GoodwinMartin A. HayesPer E. AndrénConstanze HilgendorfNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anna Nilsson Alexandra Peric Marie Strimfors Richard J. A. Goodwin Martin A. Hayes Per E. Andrén Constanze Hilgendorf Mass Spectrometry Imaging proves differential absorption profiles of well-characterised permeability markers along the crypt-villus axis
description	Abstract Knowledge about the region-specific absorption profiles from the gastrointestinal tract of orally administered drugs is a critical factor guiding dosage form selection in drug development. We have used a novel approach to study three well-characterized permeability and absorption marker drugs in the intestine. Propranolol and metoprolol (highly permeable compounds) and atenolol (low-moderate permeability compound) were orally co-administered to rats. The site of drug absorption was revealed by high spatial resolution matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) and complemented by quantitative measurement of drug concentration in tissue homogenates. MALDI-MSI identified endogenous molecular markers that illustrated the villi structures and confirmed the different absorption sites assigned to histological landmarks for the three drugs. Propranolol and metoprolol showed a rapid absorption and shorter transit distance in contrast to atenolol, which was absorbed more slowly from more distal sites. This study provides novel insights into site specific absorption for each of the compounds along the crypt-villus axis, as well as confirming a proximal-distal absorption gradient along the intestine. The combined analytical approach allowed the quantification and spatial resolution of drug distribution in the intestine and provided experimental evidence for the suggested absorption behaviour of low and highly permeable compounds.
format	article
author	Anna Nilsson Alexandra Peric Marie Strimfors Richard J. A. Goodwin Martin A. Hayes Per E. Andrén Constanze Hilgendorf
author_facet	Anna Nilsson Alexandra Peric Marie Strimfors Richard J. A. Goodwin Martin A. Hayes Per E. Andrén Constanze Hilgendorf
author_sort	Anna Nilsson
title	Mass Spectrometry Imaging proves differential absorption profiles of well-characterised permeability markers along the crypt-villus axis
title_short	Mass Spectrometry Imaging proves differential absorption profiles of well-characterised permeability markers along the crypt-villus axis
title_full	Mass Spectrometry Imaging proves differential absorption profiles of well-characterised permeability markers along the crypt-villus axis
title_fullStr	Mass Spectrometry Imaging proves differential absorption profiles of well-characterised permeability markers along the crypt-villus axis
title_full_unstemmed	Mass Spectrometry Imaging proves differential absorption profiles of well-characterised permeability markers along the crypt-villus axis
title_sort	mass spectrometry imaging proves differential absorption profiles of well-characterised permeability markers along the crypt-villus axis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/45e76ae7ec17443ea148df3403eb0c61
work_keys_str_mv	AT annanilsson massspectrometryimagingprovesdifferentialabsorptionprofilesofwellcharacterisedpermeabilitymarkersalongthecryptvillusaxis AT alexandraperic massspectrometryimagingprovesdifferentialabsorptionprofilesofwellcharacterisedpermeabilitymarkersalongthecryptvillusaxis AT mariestrimfors massspectrometryimagingprovesdifferentialabsorptionprofilesofwellcharacterisedpermeabilitymarkersalongthecryptvillusaxis AT richardjagoodwin massspectrometryimagingprovesdifferentialabsorptionprofilesofwellcharacterisedpermeabilitymarkersalongthecryptvillusaxis AT martinahayes massspectrometryimagingprovesdifferentialabsorptionprofilesofwellcharacterisedpermeabilitymarkersalongthecryptvillusaxis AT pereandren massspectrometryimagingprovesdifferentialabsorptionprofilesofwellcharacterisedpermeabilitymarkersalongthecryptvillusaxis AT constanzehilgendorf massspectrometryimagingprovesdifferentialabsorptionprofilesofwellcharacterisedpermeabilitymarkersalongthecryptvillusaxis
_version_	1718388508493611008

Mass Spectrometry Imaging proves differential absorption profiles of well-characterised permeability markers along the crypt-villus axis

Ejemplares similares