TY - JOUR

T1 - Nicotine permeability across the buccal TR146 cell culture model and porcine buccal mucosa in vitro

T2 - effect of pH and concentration

AU - Nielsen, Hanne Mørck

AU - Rassing, Margrethe Rømer

PY - 2002

Y1 - 2002

N2 - The present study was conducted to investigate and compare the effect of pH and drug concentration on nicotine permeability across the TR146 cell culture model and porcine buccal mucosa in vitro. As a further characterization of the TR146 cell culture model, it was explored whether the results were comparable for bi-directional and uni-directional transport in the presence of a transmembrane pH gradient. Nicotine concentrations between 10(-5) and 10(-2) M were applied to the apical side of the TR146 cell culture model or the mucosal side of porcine buccal mucosa. Buffers with pH values of 5.5, 7.4 and 8.1 were used to obtain different fractions of non- and mono-ionized nicotine. The apparent permeability (P(app)) of nicotine across both models increased significantly with increasing pH, and the P(app) values obtained with the two models could be correlated in a linear manner. With increasing concentrations of nicotine, the P(app) values decreased, which can partly be explained by an effect on the paracellular pathway. Similar results were also obtained when using the models for bi-directional as well as for uni-directional studies. The TR146 cell culture model may be used as model for buccal epithelium in studies with ionized drugs and a transmembrane pH gradient.

AB - The present study was conducted to investigate and compare the effect of pH and drug concentration on nicotine permeability across the TR146 cell culture model and porcine buccal mucosa in vitro. As a further characterization of the TR146 cell culture model, it was explored whether the results were comparable for bi-directional and uni-directional transport in the presence of a transmembrane pH gradient. Nicotine concentrations between 10(-5) and 10(-2) M were applied to the apical side of the TR146 cell culture model or the mucosal side of porcine buccal mucosa. Buffers with pH values of 5.5, 7.4 and 8.1 were used to obtain different fractions of non- and mono-ionized nicotine. The apparent permeability (P(app)) of nicotine across both models increased significantly with increasing pH, and the P(app) values obtained with the two models could be correlated in a linear manner. With increasing concentrations of nicotine, the P(app) values decreased, which can partly be explained by an effect on the paracellular pathway. Similar results were also obtained when using the models for bi-directional as well as for uni-directional studies. The TR146 cell culture model may be used as model for buccal epithelium in studies with ionized drugs and a transmembrane pH gradient.

KW - Animals

KW - Cell Culture Techniques

KW - Cell Line

KW - Epithelial Cells

KW - Humans

KW - Hydrogen-Ion Concentration

KW - Mouth Mucosa

KW - Nicotine

KW - Permeability

KW - Swine

M3 - Journal article

C2 - 12128169

VL - 16

SP - 151

EP - 157

JO - Norvegica Pharmaceutica Acta

JF - Norvegica Pharmaceutica Acta

SN - 0928-0987

IS - 3

ER -