Selvaratnam L, Cruchley A T, Navsaria H, Wertz P W, Hagi-Pavli E P, Leigh I M, Squier C A, Williams D M
Clinical and Diagnostic Oral Sciences, Barts and the London, Queen Mary's School of Medicine and Dentistry, Whitechapel, UK.
Oral Dis. 2001 Jul;7(4):252-8.
The aim of this study was to establish whether an in vitro model of human oral mucosa had similar permeability characteristics to normal oral mucosa. Such a model would have considerable value as an alternative to the use of mucosal biopsies in studies of transmucosal drug delivery.
Keratinocytes obtained from buccal mucosa, hard palate and abdominal skin were seeded onto inert collagen membranes (Cellagen Discs) or dead de-epidermised dermis (DDED) and grown either as submerged or air-liquid interface cultures. Subsequently the ultrastructural characteristics, permeability to water and barrier lipid content of the epithelial cultures were assessed and compared with samples of intact mucosa and skin.
All the cultures stratified into multilayered epithelia and displayed features of differentiation including tonofilaments, desmosomes and membrane coating granules. The permeability characteristics and barrier lipid content of the oral mucosal cultures resembled those of intact mucosa. By contrast, epidermal keratinocytes failed to produce a permeability barrier comparable with that of skin and had low levels of barrier associated lipids.
Cultures of human oral mucosal keratinocytes obtained from healthy adults develop similar permeability properties and barrier lipid composition to their site of origin. This model system may be useful for the evaluation of local and systemic oral mucosal drug delivery.
本研究的目的是确定人口腔黏膜的体外模型是否具有与正常口腔黏膜相似的渗透特性。这样的模型作为在经黏膜药物递送研究中替代使用黏膜活检的方法将具有相当大的价值。
从颊黏膜、硬腭和腹部皮肤获取的角质形成细胞接种到惰性胶原膜(Cellagen圆盘)或死亡的去表皮真皮(DDED)上,并分别作为浸没培养或气液界面培养生长。随后评估上皮培养物的超微结构特征、对水的渗透性和屏障脂质含量,并与完整黏膜和皮肤样本进行比较。
所有培养物均分层形成多层上皮,并表现出分化特征,包括张力丝、桥粒和膜被颗粒。口腔黏膜培养物的渗透特性和屏障脂质含量与完整黏膜相似。相比之下,表皮角质形成细胞未能产生与皮肤相当的渗透屏障,且屏障相关脂质水平较低。
从健康成年人获取的人口腔黏膜角质形成细胞培养物具有与其起源部位相似的渗透特性和屏障脂质组成。该模型系统可能有助于评估局部和全身口腔黏膜药物递送。