TY - JOUR

T1 - TR146 cells grown on filters as a model of human buccal epithelium

T2 - permeability of fluorescein isothiocyanate-labelled dextrans in the presence of sodium glycocholate

AU - Nielsen, Hanne Mørck

AU - Verhoef, J C

AU - Ponec, M

AU - Rassing, M R

PY - 1999

Y1 - 1999

N2 - The aim of the present study was to characterize the TR146 cell culture model as an in vitro model of human buccal epithelium with respect to the permeability of test substances with different molecular weights (M(w)). For this purpose, the apparent permeability (P(app)) values for mannitol and for fluorescein isothiocyanate (FITC)-labelled dextrans (FD) with various M(w) (4000-40000) were compared to the P(app) values obtained using porcine buccal mucosa as an in vitro model of the human buccal epithelium. The effect of 10 mM sodium glycocholate (GC) on the P(app) values was examined. To identify the pathways by which FD of M(w) 4000-40000 were transported, the confocal laser scanning microscope (CLSM) was used. The P(app) values obtained with the TR146 cell culture model in the absence of a permeability enhancer linearly decreased with increasing M(w) of the test substance from 0. 65+/-0.055x10(-8) to 44+/-7.5x10(-8) cm/s, as the P(app) values obtained with porcine buccal mucosa. In the presence of the permeability enhancer, GC, the permeability of the FD across the cultured TR146 cell culture model increased in a parabolic manner, reaching maximum at M(w) 10000. In the absence of the enhancer, only paracellular localization of FD was observed while, in the presence of GC, FD also could be detected in the cytosol of some of the superficial cells. The GC-induced enhancement of FD permeation may be partially attributed to changed permeation pathways. The present results indicate that the TR146 cell culture model is a suitable in vitro model for mechanistic permeability studies of human buccal drug permeability.

AB - The aim of the present study was to characterize the TR146 cell culture model as an in vitro model of human buccal epithelium with respect to the permeability of test substances with different molecular weights (M(w)). For this purpose, the apparent permeability (P(app)) values for mannitol and for fluorescein isothiocyanate (FITC)-labelled dextrans (FD) with various M(w) (4000-40000) were compared to the P(app) values obtained using porcine buccal mucosa as an in vitro model of the human buccal epithelium. The effect of 10 mM sodium glycocholate (GC) on the P(app) values was examined. To identify the pathways by which FD of M(w) 4000-40000 were transported, the confocal laser scanning microscope (CLSM) was used. The P(app) values obtained with the TR146 cell culture model in the absence of a permeability enhancer linearly decreased with increasing M(w) of the test substance from 0. 65+/-0.055x10(-8) to 44+/-7.5x10(-8) cm/s, as the P(app) values obtained with porcine buccal mucosa. In the presence of the permeability enhancer, GC, the permeability of the FD across the cultured TR146 cell culture model increased in a parabolic manner, reaching maximum at M(w) 10000. In the absence of the enhancer, only paracellular localization of FD was observed while, in the presence of GC, FD also could be detected in the cytosol of some of the superficial cells. The GC-induced enhancement of FD permeation may be partially attributed to changed permeation pathways. The present results indicate that the TR146 cell culture model is a suitable in vitro model for mechanistic permeability studies of human buccal drug permeability.

KW - Animals

KW - Cell Line

KW - Chromatography

KW - Dextrans

KW - Drug Interactions

KW - Epithelium

KW - Fluorescein

KW - Glycocholic Acid

KW - Isocyanates

KW - Mannitol

KW - Models, Biological

KW - Mouth Mucosa

KW - Mucocutaneous Lymph Node Syndrome

KW - Swine

M3 - Journal article

C2 - 10425328

VL - 60

SP - 223

EP - 233

JO - Journal of Controlled Release

JF - Journal of Controlled Release

SN - 0168-3659

IS - 2-3

ER -