TR146 cells grown on filters as a model of human buccal epithelium: permeability of fluorescein isothiocyanate-labelled dextrans in the presence of sodium glycocholate
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TR146 cells grown on filters as a model of human buccal epithelium : permeability of fluorescein isothiocyanate-labelled dextrans in the presence of sodium glycocholate. / Nielsen, Hanne Mørck; Verhoef, J C; Ponec, M; Rassing, M R.
In: Journal of Controlled Release, Vol. 60, No. 2-3, 1999, p. 223-33.Research output: Contribution to journal › Journal article › Research › peer-review
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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 -
ID: 43890818