Miyazaki Kaori, Sasaki Akira, Mizuuchi Hiroshi
DMPK Research Laboratories, Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 1000 Kamoshida, Aoba-ku, Yokohama 227-0033, Japan.
Pharmaceutics. 2023 Nov 30;15(12):2714. doi: 10.3390/pharmaceutics15122714.
Because of the increasing sophistication of formulation technology and the increasing polymerization of compounds directed toward undruggable drug targets, the influence of the mucus layer on gastrointestinal drug absorption has received renewed attention. Therefore, understanding the complex structure of the mucus layer containing highly glycosylated glycoprotein mucins, lipids bound to the mucins, and water held by glycans interacting with each other is critical. Recent advances in cell culture and engineering techniques have led to the development of evaluation systems that closely mimic the ecological environment and have been applied to the evaluation of gastrointestinal drug absorption while considering the mucus layer. This review provides a better understanding of the mucus layer components and the gastrointestinal tract's biological defense barrier, selects an assessment system for drug absorption in the mucus layer based on evaluation objectives, and discusses the overview and features of each assessment system.
由于制剂技术日益复杂,以及针对不可成药靶点的化合物聚合度不断提高,黏液层对胃肠道药物吸收的影响再次受到关注。因此,了解包含高度糖基化糖蛋白黏蛋白、与黏蛋白结合的脂质以及通过聚糖相互作用保留的水分的黏液层复杂结构至关重要。细胞培养和工程技术的最新进展促成了紧密模拟生态环境的评估系统的开发,并已应用于在考虑黏液层的情况下评估胃肠道药物吸收。本综述有助于更好地理解黏液层成分和胃肠道的生物防御屏障,根据评估目标选择黏液层药物吸收的评估系统,并讨论每个评估系统的概况和特点。