title: 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.
abstract: 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.
authors.affiliation: Department of Pharmaceutics, The Royal Danish School of Pharmacy, 2 Universitetsparken, 2100, Copenhagen, Denmark.
authors.forename: H M
authors.initials: HM
authors.lastname: Nielsen
authors.forename: M R
authors.initials: MR
authors.lastname: Rassing
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology*; D018929:Cell Culture Techniques / Q000379:methods; D002455:Cell Division; D002463:Cell Membrane Permeability / Q000187:drug effects; D002610:Cheek; D002756:Cholagogues and Choleretics / Q000494:pharmacology*; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism*; D005374:Filtration / Q000295:instrumentation; D006000:Glycocholic Acid / Q000494:pharmacology; D006002:Glycodeoxycholic Acid / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008353:Mannitol / Q000493:pharmacokinetics; D009061:Mouth Mucosa / Q000166:cytology* / Q000378:metabolism*; D009994:Osmolar Concentration; D013552:Swine; D013656:Taurocholic Acid / Q000494:pharmacology
chemical_list: D001647:Bile Acids and Salts; D002756:Cholagogues and Choleretics; D006002:Glycodeoxycholic Acid; D008353:Mannitol; D013656:Taurocholic Acid; D006000:Glycocholic Acid