Department of Pharmaceutics, School of Pharmacy, Virginia Commonwealth University, 410 N 12th St, Richmond, VA 23298, USA.
Department of Pharmaceutics, School of Pharmacy, Virginia Commonwealth University, 410 N 12th St, Richmond, VA 23298, USA.
Int J Pharm. 2022 Aug 25;624:122004. doi: 10.1016/j.ijpharm.2022.122004. Epub 2022 Jul 9.
The Caco-2 cell model has been widely used to assess the permeability of drug candidates. It has provided a high throughput in vitro platform, functionally resembling the enterocytes. Since the oral route is the most preferred for drug administration, the Caco-2 cell model acts as a very important tool to elucidate the oral "druggability" of a molecule by providing a fairly reliable estimate of its permeability through the intestinal membrane. Despite its shortcomings (the lack of a mucus layer, long cultivation period, inter-lab variability, and differences in expression of enzymes, transporters, and tight junction complexes) it remains heavily used due to its reliability, predictive performance, and wide acceptance. Various modifications have been made: co-culturing with other intestinal cells, applying biosimilar mucus, reducing culturing time, combining Caco-2 monolayer with the dissolution apparatus, enhancing protein expression, and redesigning the sampling apparatus. These modifications are intended to overcome some of the shortcomings of the Caco-2 model in order to make its use easier, quicker, economical, and more representative of the intestine. The aim of this review is to discuss such modifications to enhance this model's utility, predictive performance, and reproducibility.
Caco-2 细胞模型已被广泛用于评估候选药物的通透性。它提供了高通量的体外平台，在功能上类似于肠细胞。由于口服途径是最常用于药物给药的途径，因此 Caco-2 细胞模型通过提供对其通过肠膜通透性的相当可靠的估计，成为阐明分子口服“可用药性”的重要工具。尽管存在一些缺点（缺乏黏液层、培养周期长、实验室间变异性以及酶、转运体和紧密连接复合物表达的差异），但由于其可靠性、预测性能和广泛接受性，它仍然被广泛使用。已经进行了各种改进：与其他肠细胞共培养、应用类似生物的黏液、缩短培养时间、将 Caco-2 单层与溶解装置结合、增强蛋白质表达以及重新设计取样装置。这些改进旨在克服 Caco-2 模型的一些缺点，使其使用更加容易、快速、经济，并且更能代表肠道。本文的目的是讨论这些改进，以增强该模型的实用性、预测性能和重现性。
