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

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

N1 - Copyright © 2017. Published by Elsevier B.V.

PY - 2017/12

Y1 - 2017/12

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.

U2 - 10.1016/j.ejpb.2017.09.016

DO - 10.1016/j.ejpb.2017.09.016

M3 - Journal article

C2 - 28974436

SN - 0939-6411

VL - 121

SP - 121

EP - 128

JO - European Journal of Pharmaceutics and Biopharmaceutics

JF - European Journal of Pharmaceutics and Biopharmaceutics

ER -