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Permeability Barriers for Nicotine and Mannitol in Porcine Buccal Mucosa Studied by High-Resolution MALDI Mass Spectrometry Imaging
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2018-01-02 00:00:00 , DOI: 10.1021/acs.molpharmaceut.7b00891 Eva Marxen 1 , Jette Jacobsen 1 , Birgitte Hyrup 2 , Christian Janfelt 1
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2018-01-02 00:00:00 , DOI: 10.1021/acs.molpharmaceut.7b00891 Eva Marxen 1 , Jette Jacobsen 1 , Birgitte Hyrup 2 , Christian Janfelt 1
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Improved nicotine permeability across buccal mucosa may enable more effective oromucosal nicotine replacement therapy products. It is essential to know the location and composition of the main barrier for drug diffusion to enhance the drug permeability. Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI MSI) is a rapidly evolving technique that can be used to image the spatial distribution of drugs and drug metabolites in tissue cryo-sections, without prior labeling of the drug. In this study, the distribution of nicotine and mannitol in porcine buccal mucosa was imaged with 10 μm spatial resolution after apical as well as submucosal application of the drugs in order to localize the main permeability barrier(s). This was supported by ex vivo permeability studies across separated porcine buccal epithelium and submucosa. Lastly, the metabolism of nicotine in porcine buccal mucosa was evaluated by imaging of the main metabolite, cotinine. The results showed that the main permeability barrier to both nicotine and mannitol was located in the outer fourth of the epithelium. Further, it was shown that cotinine was sparsely distributed in excised porcine buccal mucosa, indicating that nicotine metabolism in excised porcine buccal mucosa was negligible. MALDI MSI was shown to be a useful method for imaging spatial distribution of drugs in buccal mucosa.
中文翻译：
高分辨率MALDI质谱成像研究猪颊黏膜中尼古丁和甘露醇的渗透屏障
跨颊粘膜的尼古丁渗透性提高，可能使口腔粘膜尼古丁替代治疗产品更加有效。了解药物扩散的主要屏障的位置和组成以增强药物渗透性至关重要。基质辅助激光解吸电离质谱成像（MALDI MSI）是一项快速发展的技术，可用于对组织冷冻切片中药物和药物代谢产物的空间分布进行成像，而无需事先标记药物。在这项研究中，尼古丁和甘露醇在猪颊黏膜中的分布以10μm的空间分辨率成像，在药物的顶端和黏膜下施用后可以定位主要的渗透屏障。这得到了离体的支持分离的猪颊粘膜上皮和粘膜下层的通透性研究。最后，通过主要代谢产物可替宁的成像评估了猪颊粘膜中尼古丁的代谢。结果表明，尼古丁和甘露醇的主要通透性屏障位于上皮的外四分之一处。此外，显示可替宁稀疏地分布在切除的猪颊粘膜中，表明切除的猪颊粘膜中的尼古丁代谢可忽略不计。MALDI MSI被证明是对颊粘膜药物空间分布进行成像的有用方法。
更新日期：2018-01-02
中文翻译：
高分辨率MALDI质谱成像研究猪颊黏膜中尼古丁和甘露醇的渗透屏障
跨颊粘膜的尼古丁渗透性提高，可能使口腔粘膜尼古丁替代治疗产品更加有效。了解药物扩散的主要屏障的位置和组成以增强药物渗透性至关重要。基质辅助激光解吸电离质谱成像（MALDI MSI）是一项快速发展的技术，可用于对组织冷冻切片中药物和药物代谢产物的空间分布进行成像，而无需事先标记药物。在这项研究中，尼古丁和甘露醇在猪颊黏膜中的分布以10μm的空间分辨率成像，在药物的顶端和黏膜下施用后可以定位主要的渗透屏障。这得到了离体的支持分离的猪颊粘膜上皮和粘膜下层的通透性研究。最后，通过主要代谢产物可替宁的成像评估了猪颊粘膜中尼古丁的代谢。结果表明，尼古丁和甘露醇的主要通透性屏障位于上皮的外四分之一处。此外，显示可替宁稀疏地分布在切除的猪颊粘膜中，表明切除的猪颊粘膜中的尼古丁代谢可忽略不计。MALDI MSI被证明是对颊粘膜药物空间分布进行成像的有用方法。
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