Mucin dispersions as a model for the oromucosal mucus layer in in vitro and ex vivo buccal permeability studies of small molecules

Eva Marxen, Mette Dalskov Mosgaard, Anne Marie Lynge Pedersen, Jette Jacobsen*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

The mucus layer is believed to play a part in drug permeation across the oral mucosa. Human freeze-dried saliva (HFDS) and porcine gastric mucin (PGM) was evaluated as model for mucus layer per se or in conjunction with in vitro and ex vivo buccal permeability models. Four small molecules (nicotine, mannitol, propranolol, caffeine) showed decreased permeability across mucin dispersions, compared to controls, and a greater effect was seen with HFDS than with PGM. Permeability of propranolol and caffeine across filter-grown TR146 cells was decreased by the presence of mucin, whereas no effect was found on nicotine and mannitol. Incubation of porcine buccal mucosa with mucin dispersions for 24 h compromised the integrity of the tissue, whereas 30 min incubation did not affect tissue integrity. Tissue incubation with mucin dispersions did not decrease nicotine permeability. For the studied model drugs, it is concluded that mucin dispersions constitute a minor barrier for drug diffusion compared to the epithelium.

Original languageEnglish
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume121
Pages (from-to)121-128
Number of pages8
ISSN0939-6411
DOIs
Publication statusPublished - 1 Dec 2017

Keywords

  • Absorption
  • Barrier
  • Buccal drug delivery
  • Drug diffusion
  • Mucus
  • Permeability
  • Small molecules

Cite this

@article{010d91cba92a4b78ab5accbb8dba9c11,
title = "Mucin dispersions as a model for the oromucosal mucus layer in in vitro and ex vivo buccal permeability studies of small molecules",
abstract = "The mucus layer is believed to play a part in drug permeation across the oral mucosa. Human freeze-dried saliva (HFDS) and porcine gastric mucin (PGM) was evaluated as model for mucus layer per se or in conjunction with in vitro and ex vivo buccal permeability models. Four small molecules (nicotine, mannitol, propranolol, caffeine) showed decreased permeability across mucin dispersions, compared to controls, and a greater effect was seen with HFDS than with PGM. Permeability of propranolol and caffeine across filter-grown TR146 cells was decreased by the presence of mucin, whereas no effect was found on nicotine and mannitol. Incubation of porcine buccal mucosa with mucin dispersions for 24 h compromised the integrity of the tissue, whereas 30 min incubation did not affect tissue integrity. Tissue incubation with mucin dispersions did not decrease nicotine permeability. For the studied model drugs, it is concluded that mucin dispersions constitute a minor barrier for drug diffusion compared to the epithelium.",
keywords = "Absorption, Barrier, Buccal drug delivery, Drug diffusion, Mucus, Permeability, Small molecules",
author = "Eva Marxen and Mosgaard, {Mette Dalskov} and Pedersen, {Anne Marie Lynge} and Jette Jacobsen",
year = "2017",
month = "12",
day = "1",
doi = "10.1016/j.ejpb.2017.09.016",
language = "English",
volume = "121",
pages = "121--128",
journal = "European Journal of Pharmaceutics and Biopharmaceutics",
issn = "0939-6411",
publisher = "Elsevier",

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Mucin dispersions as a model for the oromucosal mucus layer in in vitro and ex vivo buccal permeability studies of small molecules. / Marxen, Eva; Mosgaard, Mette Dalskov; Pedersen, Anne Marie Lynge; Jacobsen, Jette.

In: European Journal of Pharmaceutics and Biopharmaceutics, Vol. 121, 01.12.2017, p. 121-128.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Mucin dispersions as a model for the oromucosal mucus layer in in vitro and ex vivo buccal permeability studies of small molecules

AU - Marxen, Eva

AU - Mosgaard, Mette Dalskov

AU - Pedersen, Anne Marie Lynge

AU - Jacobsen, Jette

PY - 2017/12/1

Y1 - 2017/12/1

N2 - The mucus layer is believed to play a part in drug permeation across the oral mucosa. Human freeze-dried saliva (HFDS) and porcine gastric mucin (PGM) was evaluated as model for mucus layer per se or in conjunction with in vitro and ex vivo buccal permeability models. Four small molecules (nicotine, mannitol, propranolol, caffeine) showed decreased permeability across mucin dispersions, compared to controls, and a greater effect was seen with HFDS than with PGM. Permeability of propranolol and caffeine across filter-grown TR146 cells was decreased by the presence of mucin, whereas no effect was found on nicotine and mannitol. Incubation of porcine buccal mucosa with mucin dispersions for 24 h compromised the integrity of the tissue, whereas 30 min incubation did not affect tissue integrity. Tissue incubation with mucin dispersions did not decrease nicotine permeability. For the studied model drugs, it is concluded that mucin dispersions constitute a minor barrier for drug diffusion compared to the epithelium.

AB - The mucus layer is believed to play a part in drug permeation across the oral mucosa. Human freeze-dried saliva (HFDS) and porcine gastric mucin (PGM) was evaluated as model for mucus layer per se or in conjunction with in vitro and ex vivo buccal permeability models. Four small molecules (nicotine, mannitol, propranolol, caffeine) showed decreased permeability across mucin dispersions, compared to controls, and a greater effect was seen with HFDS than with PGM. Permeability of propranolol and caffeine across filter-grown TR146 cells was decreased by the presence of mucin, whereas no effect was found on nicotine and mannitol. Incubation of porcine buccal mucosa with mucin dispersions for 24 h compromised the integrity of the tissue, whereas 30 min incubation did not affect tissue integrity. Tissue incubation with mucin dispersions did not decrease nicotine permeability. For the studied model drugs, it is concluded that mucin dispersions constitute a minor barrier for drug diffusion compared to the epithelium.

KW - Absorption

KW - Barrier

KW - Buccal drug delivery

KW - Drug diffusion

KW - Mucus

KW - Permeability

KW - Small molecules

U2 - 10.1016/j.ejpb.2017.09.016

DO - 10.1016/j.ejpb.2017.09.016

M3 - Journal article

VL - 121

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JO - European Journal of Pharmaceutics and Biopharmaceutics

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SN - 0939-6411

ER -