Department of Chemical Engineering and Materials Science, Wayne State University, Detroit, Michigan 48202, USA.
J Mater Chem B. 2019 Nov 7;7(41):6310-6320. doi: 10.1039/c9tb01081e. Epub 2019 Jul 31.
The active pharmaceutical ingredients (APIs) have to cross the natural barriers and get into the blood to impart the pharmacological effects. The tight junctions (TJs) between the epithelial cells serve as the major selectively permeable barriers and control the paracellular transport of the majority of hydrophilic drugs, in particular, peptides and proteins. TJs perfectly balance the targeted transport and the exclusion of other unexpected pathogens under the normal conditions. Many biomaterials have shown the capability to open the TJs and improve the oral bioavailability and targeting efficacy of the APIs. Nevertheless, there is limited understanding of the biomaterial-TJ interactions. The opening of the TJs further poses the risk of autoimmune diseases and infections. This review article summarizes the most updated literature and presents insights into the TJ structure, the biomaterial-TJ interaction mechanism, the benefits and drawbacks of TJ disruption, and methods for evaluating such interactions.
活性药物成分 (APIs) 必须穿过天然屏障进入血液,才能发挥药理作用。上皮细胞之间的紧密连接 (TJs) 作为主要的选择性渗透屏障,控制大多数亲水性药物(特别是肽和蛋白质)的细胞旁转运。在正常情况下,TJs 完美地平衡了靶向运输和对其他意外病原体的排斥。许多生物材料已显示出打开 TJs 的能力,并提高了 APIs 的口服生物利用度和靶向效果。然而,对于生物材料-TJ 相互作用的理解还很有限。TJ 的打开进一步带来了自身免疫性疾病和感染的风险。本文综述了最新的文献,介绍了 TJ 的结构、生物材料-TJ 相互作用机制、TJ 破坏的益处和缺点,以及评估这种相互作用的方法。