Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, Australia.
Pharm Res. 2018 Feb 21;35(3):70. doi: 10.1007/s11095-017-2332-y.
The purpose of this study was to assess the effect of several chemical permeation enhancers on the buccal permeability of nicotine and to image the spatial distribution of nicotine in buccal mucosa with and without buccal permeation enhancers.
The impact of sodium taurodeoxycholate (STDC), sodium dodecyl sulphate (SDS), dimethyl sulfoxide (DMSO) and Azone® on the permeability of [H]-nicotine and [C]-mannitol (a paracellular marker) across porcine buccal mucosa was studied ex vivo in modified Ussing chambers. The distribution of nicotine, mannitol and permeation enhancers was imaged using using matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI MSI).
Despite STDC significantly increasing permeability of [C]-mannitol, no enhancing effect was seen on [H]-nicotine permeability with any of the permeation enhancers. Rather, SDS and DMSO retarded nicotine permeability, likely due to nicotine being retained in the donor compartment. The permeability results were complemented by the spatial distribution of nicotine and mannitol determined with MALDI MSI.
The buccal permeability of nicotine was affected in an enhancer specific manner, suggesting that nicotine primarily diffuses via the transcellular pathway. MALDI MSI was shown to complement ex vivo permeability studies and to be a useful qualitative tool for visualizing drug and penetration enhancer distribution in buccal mucosa.
本研究旨在评估几种化学渗透增强剂对尼古丁颊黏膜透过性的影响，并利用图像技术观察有/无颊黏膜渗透增强剂时尼古丁在颊黏膜中的空间分布。
本研究采用改良的 Ussing 室体外实验方法，评估牛磺胆酸钠（STDC）、十二烷基硫酸钠（SDS）、二甲基亚砜（DMSO）和 Azone® 对 [H]-尼古丁和 [C]-甘露醇（一种细胞旁标记物）透过猪颊黏膜的渗透作用。利用基质辅助激光解吸电离质谱成像（MALDI MSI）技术对尼古丁、甘露醇和渗透增强剂的分布进行成像。
尽管 STDC 显著增加了 [C]-甘露醇的透过性，但任何渗透增强剂对 [H]-尼古丁的透过性均无增强作用。相反，SDS 和 DMSO 会减缓尼古丁的透过性，这可能是由于尼古丁被保留在供体腔内。MALDI MSI 确定的尼古丁和甘露醇的空间分布结果补充了渗透实验结果。
尼古丁的颊黏膜透过性以增强剂特异性的方式受到影响，这表明尼古丁主要通过细胞旁路扩散。MALDI MSI 可补充体外渗透研究，并可作为可视化颊黏膜中药物和渗透增强剂分布的有用定性工具。
