TR146 cells grown on filters as a model of human buccal epithelium: III. Permeability enhancement by different pH values, different osmolality values, and bile salts

TY - JOUR

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

T2 - III. Permeability enhancement by different pH values, different osmolality values, and bile salts

AU - Nielsen, Hanne Mørck

AU - Rassing, M R

PY - 1999

Y1 - 1999

N2 - The aim of the present study was to evaluate the TR146 cell culture model as an in vitro model of human buccal epithelium with respect to the permeability enhancement by different pH values, different osmolality values or bile salts. For this purpose, the increase in the apparent permeability (P(app)) of the hydrophilic marker mannitol due to exposure to solutions with pH values or osmolality values different from the physiological values was studied. As in studies with solutions of either taurocholate (TC), glycocholate (GC) or glycodeoxycholate (GDC) the results were compared to the increase in P(app) of mannitol obtained in analog studies using porcine buccal mucosa in an Ussing chamber. The effect of the exposure on the electrical resistance of the TR146 cell culture model and the porcine buccal mucosa was measured, and the degree of protein leakage due to GC exposure was investigated in the TR146 cell culture model. The porcine buccal mucosa was approximately ten times less permeable to mannitol than the TR146 cell culture model. The P(app)TC. Increased P(app) values correlated with a decrease in the electrical resistance of the TR146 cell culture model and the porcine buccal mucosa. GC was shown to induce concentration dependent protein leakage in the TR146 cell culture but only from the site of application, and the results indicate that duration of exposure further than 120 min was of minor importance. The present results indicate that the TR146 cell culture model may be a suitable in vitro model for efficacy studies and mechanistic studies of enhancers with potential use in human buccal drug delivery.

AB - The aim of the present study was to evaluate the TR146 cell culture model as an in vitro model of human buccal epithelium with respect to the permeability enhancement by different pH values, different osmolality values or bile salts. For this purpose, the increase in the apparent permeability (P(app)) of the hydrophilic marker mannitol due to exposure to solutions with pH values or osmolality values different from the physiological values was studied. As in studies with solutions of either taurocholate (TC), glycocholate (GC) or glycodeoxycholate (GDC) the results were compared to the increase in P(app) of mannitol obtained in analog studies using porcine buccal mucosa in an Ussing chamber. The effect of the exposure on the electrical resistance of the TR146 cell culture model and the porcine buccal mucosa was measured, and the degree of protein leakage due to GC exposure was investigated in the TR146 cell culture model. The porcine buccal mucosa was approximately ten times less permeable to mannitol than the TR146 cell culture model. The P(app)TC. Increased P(app) values correlated with a decrease in the electrical resistance of the TR146 cell culture model and the porcine buccal mucosa. GC was shown to induce concentration dependent protein leakage in the TR146 cell culture but only from the site of application, and the results indicate that duration of exposure further than 120 min was of minor importance. The present results indicate that the TR146 cell culture model may be a suitable in vitro model for efficacy studies and mechanistic studies of enhancers with potential use in human buccal drug delivery.

KW - Animals

KW - Bile Acids and Salts

KW - Cell Culture Techniques

KW - Cell Division

KW - Cell Membrane Permeability

KW - Cheek

KW - Cholagogues and Choleretics

KW - Epithelial Cells

KW - Filtration

KW - Glycocholic Acid

KW - Glycodeoxycholic Acid

KW - Humans

KW - Hydrogen-Ion Concentration

KW - Mannitol

KW - Mouth Mucosa

KW - Osmolar Concentration

KW - Swine

KW - Taurocholic Acid

M3 - Journal article

C2 - 10460917

SN - 0378-5173

VL - 185

SP - 215

EP - 225

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

IS - 2

ER -