Journal of Controlled Release 60 (1999) 223–233 TR146 cells grown on filters as a model of human buccal epithelium: permeability of fluorescein isothiocyanate-labelled dextrans in the presence of sodium glycocholate a b c Hanne Mørck Nielsen , J. Coos Verhoef , Maria Ponec , Margrethe a, * Rømer Rassing a Department of Pharmaceutics, The Royal Danish School of Pharmacy,2 Universitetsparken, 2100 Copenhagen Ø, Denmark b Department of Pharmaceutical Technology, Leiden / Amsterdam Center for Drug Research, Leiden University, 2300 RA Leiden, The Netherlands c Department of Dermatology, University Leiden Medical Center, 2300 RC Leiden, The Netherlands Received 11 May 1998; received in revised form 8 February 1999; accepted 3 March 1999 Abstract 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 ). For this purpose, the w apparent permeability (P ) values for mannitol and for fluorescein isothiocyanate (FITC)-labelled dextrans (FD) with app various M (4000–40 000) were compared to the P values obtained using porcine buccal mucosa as an in vitro model of w app the human buccal epithelium. The effect of 10 mM sodium glycocholate (GC) on the P values was examined. To identify app the pathways by which FD of M 4000–40 000 were transported, the confocal laser scanning microscope (CLSM) was used. w The P values obtained with the TR146 cell culture model in the absence of a permeability enhancer linearly decreased app 28 28 with increasing M of the test substance from 0.6560.055 310 to 4467.5 310 cm/s, as the P values obtained with w app 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 10 000. In the absence of the enhancer, w 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.  1999 Elsevier Science B.V. All rights reserved. Keywords: TR146 cell culture model; Buccal permeability; Molecular weight; Confocal microscopy; Permeability enhancement 1. Introduction advantages over oral drug delivery, most important is the avoidance of hepatic and gastrointestinal first- pass metabolism. This is of particular interest with Buccal administration of drugs offers several regard to peptide and protein drugs, most of which are presently administered by injection. Since pep- *Corresponding author. Tel.: 145-35-370-850 ext. 233; fax: tides and proteins are hydrophilic molecules with a 145-35-371-277. E-mail address: mrr@mail.dfh.dk (M.R. Rassing) relatively high molecular weight ( M ), the mecha- w 0168-3659 / 99 / $ – see front matter  1999 Elsevier Science B.V. All rights reserved. PII: S0168-3659(99)00081-4