Steric and interactive barrier properties of intestinal mucus elucidated by particle diffusion and peptide permeation

Marie Bøgh; María García-Díaz; Anette Müllertz; Hanne Mørck Nielsen

doi:10.1016/j.ejpb.2015.01.014

Steric and interactive barrier properties of intestinal mucus elucidated by particle diffusion and peptide permeation

Marie Bøgh, María García-Díaz, Anette Müllertz, Hanne Mørck Nielsen

28 Citations (Scopus)

Abstract

The mucus lining of the gastrointestinal tract epithelium is recognized as a barrier to efficient oral drug delivery. Recently, a new in vitro model for assessment of drug permeation across intestinal mucosa was established by applying a biosimilar mucus matrix to the surface of Caco-2 cell monolayers. The aim of the present study was to gain more insight into the steric and interactive barrier properties of intestinal mucus by studying the permeation of peptides and model compounds across the biosimilar mucus as well as across porcine intestinal mucus (PIM). As PIM disrupted the Caco-2 cell monolayers, a cell-free mucus barrier model was implemented in the studies. Both the biosimilar mucus and the PIM reduced the permeation of the selected peptide drugs to varying degrees illustrating the interactive properties of both mucus matrices. The reduction in peptide permeation was decreased depending on the cationicity and H-bonding capacity of the permeant clearly demonstrated by using the biosimilar mucus, whereas the larger inter sample variation of the PIM matrix obstructed similarly clear conclusions. Thus, for mechanistic studies of permeation across mucus and mucosa the biosimilar mucus offers a relevant and reproducible alternative to native mucus.

Original language	English
Journal	European Journal of Pharmaceutics and Biopharmaceutics
Volume	94
Issue number	Part A
Pages (from-to)	136–143
Number of pages	8
ISSN	0939-6411
DOIs	https://doi.org/10.1016/j.ejpb.2015.01.014
Publication status	Published - 1 Sept 2015

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Steric and interactive barrier properties of intestinal mucus elucidated by particle diffusion and peptide permeation. / Bøgh, Marie; García-Díaz, María; Müllertz, Anette et al.
In: European Journal of Pharmaceutics and Biopharmaceutics, Vol. 94, No. Part A, 01.09.2015, p. 136–143.

Research output: Contribution to journal › Journal article › Research › peer-review

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title = "Steric and interactive barrier properties of intestinal mucus elucidated by particle diffusion and peptide permeation",

abstract = "The mucus lining of the gastrointestinal tract epithelium is recognized as a barrier to efficient oral drug delivery. Recently, a new in vitro model for assessment of drug permeation across intestinal mucosa was established by applying a biosimilar mucus matrix to the surface of Caco-2 cell monolayers. The aim of the present study was to gain more insight into the steric and interactive barrier properties of intestinal mucus by studying the permeation of peptides and model compounds across the biosimilar mucus as well as across porcine intestinal mucus (PIM). As PIM disrupted the Caco-2 cell monolayers, a cell-free mucus barrier model was implemented in the studies. Both the biosimilar mucus and the PIM reduced the permeation of the selected peptide drugs to varying degrees illustrating the interactive properties of both mucus matrices. The reduction in peptide permeation was decreased depending on the cationicity and H-bonding capacity of the permeant clearly demonstrated by using the biosimilar mucus, whereas the larger inter sample variation of the PIM matrix obstructed similarly clear conclusions. Thus, for mechanistic studies of permeation across mucus and mucosa the biosimilar mucus offers a relevant and reproducible alternative to native mucus.",

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AU - Bøgh, Marie

AU - García-Díaz, María

AU - Müllertz, Anette

AU - Nielsen, Hanne Mørck

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N2 - The mucus lining of the gastrointestinal tract epithelium is recognized as a barrier to efficient oral drug delivery. Recently, a new in vitro model for assessment of drug permeation across intestinal mucosa was established by applying a biosimilar mucus matrix to the surface of Caco-2 cell monolayers. The aim of the present study was to gain more insight into the steric and interactive barrier properties of intestinal mucus by studying the permeation of peptides and model compounds across the biosimilar mucus as well as across porcine intestinal mucus (PIM). As PIM disrupted the Caco-2 cell monolayers, a cell-free mucus barrier model was implemented in the studies. Both the biosimilar mucus and the PIM reduced the permeation of the selected peptide drugs to varying degrees illustrating the interactive properties of both mucus matrices. The reduction in peptide permeation was decreased depending on the cationicity and H-bonding capacity of the permeant clearly demonstrated by using the biosimilar mucus, whereas the larger inter sample variation of the PIM matrix obstructed similarly clear conclusions. Thus, for mechanistic studies of permeation across mucus and mucosa the biosimilar mucus offers a relevant and reproducible alternative to native mucus.

AB - The mucus lining of the gastrointestinal tract epithelium is recognized as a barrier to efficient oral drug delivery. Recently, a new in vitro model for assessment of drug permeation across intestinal mucosa was established by applying a biosimilar mucus matrix to the surface of Caco-2 cell monolayers. The aim of the present study was to gain more insight into the steric and interactive barrier properties of intestinal mucus by studying the permeation of peptides and model compounds across the biosimilar mucus as well as across porcine intestinal mucus (PIM). As PIM disrupted the Caco-2 cell monolayers, a cell-free mucus barrier model was implemented in the studies. Both the biosimilar mucus and the PIM reduced the permeation of the selected peptide drugs to varying degrees illustrating the interactive properties of both mucus matrices. The reduction in peptide permeation was decreased depending on the cationicity and H-bonding capacity of the permeant clearly demonstrated by using the biosimilar mucus, whereas the larger inter sample variation of the PIM matrix obstructed similarly clear conclusions. Thus, for mechanistic studies of permeation across mucus and mucosa the biosimilar mucus offers a relevant and reproducible alternative to native mucus.

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SP - 136

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JO - European Journal of Pharmaceutics and Biopharmaceutics

JF - European Journal of Pharmaceutics and Biopharmaceutics

IS - Part A

ER -

Steric and interactive barrier properties of intestinal mucus elucidated by particle diffusion and peptide permeation

Abstract

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