Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, Copenhagen, Denmark.
Department of Odontology, Faculty of Health and Medical Sciences, University of Copenhagen, Nørre Allé 20, Copenhagen, Denmark.
Eur J Pharm Biopharm. 2017 Dec;121:121-128. doi: 10.1016/j.ejpb.2017.09.016. Epub 2017 Sep 30.
The mucus layer is believed to play a part in drug permeation across the oral mucosa. Human freeze-dried saliva (HFDS) and porcine gastric mucin (PGM) was evaluated as model for mucus layer per se or in conjunction with in vitro and ex vivo buccal permeability models. Four small molecules (nicotine, mannitol, propranolol, caffeine) showed decreased permeability across mucin dispersions, compared to controls, and a greater effect was seen with HFDS than with PGM. Permeability of propranolol and caffeine across filter-grown TR146 cells was decreased by the presence of mucin, whereas no effect was found on nicotine and mannitol. Incubation of porcine buccal mucosa with mucin dispersions for 24 h compromised the integrity of the tissue, whereas 30 min incubation did not affect tissue integrity. Tissue incubation with mucin dispersions did not decrease nicotine permeability. For the studied model drugs, it is concluded that mucin dispersions constitute a minor barrier for drug diffusion compared to the epithelium.
黏液层被认为在药物经口腔黏膜渗透中发挥作用。人冻干唾液（HFDS）和猪胃黏蛋白（PGM）被评估为黏液层本身或与体外和体内颊黏膜渗透模型联合使用的模型。与对照相比，四种小分子（尼古丁、甘露醇、普萘洛尔、咖啡因）在黏液分散体中的渗透性降低，HFDS 比 PGM 的效果更大。黏蛋白的存在降低了普萘洛尔和咖啡因穿过过滤培养的 TR146 细胞的渗透性，而尼古丁和甘露醇则没有影响。用黏液分散体孵育猪颊黏膜 24 小时会损害组织的完整性，而 30 分钟的孵育则不会影响组织的完整性。黏液分散体孵育不会降低尼古丁的渗透性。对于所研究的模型药物，可以得出结论，与上皮相比，黏液分散体对药物扩散构成较小的屏障。
