Laboratory of Bio-Functional Molecular Chemistry, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan.
Curr Pharm Des. 2011;17(25):2699-703. doi: 10.2174/138161211797416084.
The first step in drug absorption is the passage of drug molecules across epithelial cell sheets. Epithelial cell sheets are pivotal for the maintenance of homeostasis in the body by acting as a biological barrier that separates the inside of the body from the outside environment. Intercellular space between the adjacent epithelial cells is tightly sealed by tight junctions (TJs), which prevent solutes from freely moving across the epithelial cell sheets. Modulation of the TJ barrier has been a potent strategy for drug absorption. Absorption enhancers have been investigated since the 1980s, and sodium caprate is clinically used as an absorption enhancer. However, the biochemical constituents and structures of TJs were not elucidated until 1993. Occludin, a tetra-transmembrane protein, was identified to be a structural component of TJs in 1993. Claudin, another tetra-transmembrane protein, was identified as a structural and functional component of TJs in 1998. Modulation of occludin- or claudin-barrier is novel methods to enhance drug absorption. Recently, synthetic TJ-binding peptides, a kinase of claudin and peptide fragments of toxins have been developed. In the present review, we summarize the recent progress in TJ-modulating peptides and discuss their potencies.
药物吸收的第一步是药物分子穿过上皮细胞层。上皮细胞层通过充当将体内与外部环境分开的生物屏障，对于维持体内平衡至关重要。相邻上皮细胞之间的细胞间隙由紧密连接（TJ）紧密密封，防止溶质自由穿过上皮细胞层。调节 TJ 屏障已成为药物吸收的有效策略。自 20 世纪 80 年代以来，一直在研究吸收增强剂，并且辛酸纳已在临床上用作吸收增强剂。但是，直到 1993 年才阐明 TJ 的生化成分和结构。1993 年发现封闭蛋白是 TJ 的结构组成部分，这是一种四跨膜蛋白。 Claudin 是另一种四跨膜蛋白，于 1998 年被鉴定为 TJ 的结构和功能组成部分。调节封闭蛋白或紧密连接蛋白屏障是增强药物吸收的新方法。最近，已经开发出了合成 TJ 结合肽，claudin 的激酶和毒素的肽片段。在本综述中，我们总结了 TJ 调节肽的最新进展，并讨论了它们的效力。
