研究动态
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用于评估药物渗透性的短 Caco-2 模型:戊酸钠辅助方法。

Short Caco-2 model for evaluation of drug permeability: A sodium valerate-assisted approach.

发表日期:2024 Jul 01
作者: Naveed Ur Rehman, Seong-Ah Shin, Chang Sup Lee, Miyoung Song, Hyun Joon Kim, Hye Jin Chung
来源: INTERNATIONAL JOURNAL OF PHARMACEUTICS

摘要:

人结直肠腺癌细胞系 Caco-2 广泛用于研究肠道药物渗透性,通常在渗透性过滤器支架上生长,并在频繁更换培养基的情况下在 21 天内成熟。该过程是劳动密集型的,容易受到污染,并且产量低,导致总体使用成本较高。建立低成本、高通量、短持续时间模型的努力遇到了障碍,例如较弱的紧密连接导致单层渗漏、不完全分化导致转运蛋白表达低、复杂且具有挑战性的方案以及细胞毒性,限制了可用性。因此,本研究旨在通过定制培养基和寻找安全的分化诱导剂来解决上述问题,从而开发低成本、高效且短持续时间的模型。我们使用戊酸钠生成了一个新的快速模型,与 21 天模型相比,该模型表现出足够的转运蛋白活性、改善的单层完整性和更高水平的分化标记物。此外,当用于评估多天重复使用的药物渗透性时,该模型表现出一致且可靠的结果。这项研究证明了戊酸钠辅助简化模型在药物渗透性评估方面的潜力,具有经济和实用的优势。版权所有 © 2024 Elsevier B.V. 保留所有权利。
The human colorectal adenocarcinoma cell line Caco-2, widely used for studying intestinal drug permeability, is typically grown on permeable filter supports and matures in 21 days with frequent media changes. The process is labor-intensive, prone to contamination, and has low throughput, contributing to the overall high utilization cost. Efforts to establish a low-cost, high-throughput, short-duration model have encountered obstacles, such as weaker tight junctions causing monolayer leaks, incomplete differentiation resulting in low transporter expression, intricate and challenging protocols, and cytotoxicity, limiting the usability. Hence, this study aimed to develop a low-cost, efficient, and short-duration model by addressing the aforementioned concerns by customizing the media and finding a safe differentiation inducer. We generated a new rapid model using sodium valerate, which demonstrated sufficient transporter activity, improved monolayer integrity, and higher levels of differentiation markers than the 21-day model. Furthermore, this model exhibited consistent and reliable results when used to evaluate drug permeability over multiple days of repeated use. This study demonstrates the potential of a sodium valerate-assisted abbreviated model for drug permeability assessment with economic and practical advantages.Copyright © 2024 Elsevier B.V. All rights reserved.