Permeability barrier properties of oral keratinocyte cultures: a model of intact human oral mucosa

OBJECTIVES: The aim of this study was to establish whether an in vitro mode l of human oral mucosa had similar permeability characteristics to normal o ral mucosa. Such a model would have considerable value as an alternative to the use of mucosal biopsies in studies of transmucosal drug delivery. MATERIALS AND METHODS: Keratinocytes obtained from buccal mucosa, hard pala te and abdominal skin were seeded onto inert collagen membranes (Cellagen D iscs) or dead de-epidermised dermis (DDED) and grown either as submerged or air-liquid interface cultures. Subsequently the ultrastructural characteri stics, permeability to water and barrier lipid content of the epithelial cu ltures were assessed and compared with samples of intact mucosa and skin. RESULTS: All the cultures stratified into multilayered epithelia and displa yed features of differentiation including tonofilaments, desmosomes and mem brane coating granules. The permeability characteristics and barrier lipid content of the oral mucosal cultures resembled those of intact mucosa. By c ontrast, epidermal keratinocytes failed to produce a permeability barrier c omparable with that of skin and had low levels of barrier associated lipids . CONCLUSIONS: Cultures of human oral mucosal keratinocytes obtained from hea lthy adults develop similar permeability properties and barrier lipid compo sition to their site of origin. This model system may be useful for the eva luation of local and systemic oral mucosal drug delivery.