Furubayashi Tomoyuki, Inoue Daisuke, Kimura Shunsuke, Tanaka Akiko, Sakane Toshiyasu
Department of Pharmaceutical Technology, Kobe Pharmaceutical University, 4-19-1 Motoyamakitamachi, Higashinada-ku, Kobe 658-8558, Japan.
School of Pharmacy, Shujitsu University, 1-6-1 Nishigawara, Naka-ku, Okayama 703-8516, Japan.
Pharmaceutics. 2021 Aug 30;13(9):1363. doi: 10.3390/pharmaceutics13091363.
A well-developed lymphatic network is located under the nasal mucosa, and a few drugs that permeate the nasal mucosa are absorbed into the lymphatic capillaries. Lymph from the nasal cavity flows to the cervical lymph nodes (CLNs). In this study, we evaluated the pharmacokinetics of the direct transport of intranasally administered drugs to CLNs through the nasal mucosa of Wistar rats using methotrexate as a model drug. The drug targeting index, which was calculated based on the areas under the concentration-time curves after intravenous and intranasal administration, was 3.78, indicating the benefits of nasal delivery of methotrexate to target CLNs. The direct transport percentage, which was indicative of the contribution of the direct nose-CLN pathway of methotrexate after intranasal administration, was 74.3%. The rate constant of methotrexate from the nasal cavity to CLNs was 0.0047 ± 0.0013 min, while that from systemic circulation to CLNs was 0.0021 ± 0.0009 min. Through pharmacokinetic analysis, this study demonstrated that the direct nasal-CLN pathway contributed more to the transport of methotrexate to the CLNs than the direct blood-CLN pathway.
在鼻黏膜下方有一个发育良好的淋巴网络，一些渗透过鼻黏膜的药物会被吸收进入毛细淋巴管。鼻腔内的淋巴液流向颈淋巴结（CLNs）。在本研究中，我们以甲氨蝶呤作为模型药物，评估了经鼻给药的药物通过Wistar大鼠鼻黏膜直接转运至颈淋巴结的药代动力学。根据静脉注射和经鼻给药后的浓度 - 时间曲线下面积计算得出的药物靶向指数为3.78，表明经鼻给药甲氨蝶呤靶向颈淋巴结具有优势。经鼻给药后，甲氨蝶呤直接经鼻 - 颈淋巴结途径的贡献的直接转运百分比为74.3%。甲氨蝶呤从鼻腔到颈淋巴结的速率常数为0.0047±0.0013分钟，而从体循环到颈淋巴结的速率常数为0.0021±0.0009分钟。通过药代动力学分析，本研究表明，甲氨蝶呤经鼻 - 颈淋巴结直接途径对其转运至颈淋巴结的贡献大于经血液 - 颈淋巴结直接途径。
