Usability of Polydimethylsiloxane-Based Microfluidic Devices in Pharmaceutical Research Using Human Hepatocytes
Usability of Polydimethylsiloxane-Based Microfluidic Devices in Pharmaceutical Research Using Human Hepatocytes
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DOI：
10.1021/acsbiomaterials.1c00642
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发表时间：
2021-07-20
影响因子：
5.8
通讯作者：
Takayama, Kazuo
中科院分区：
文献类型：
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作者：
Deguchi, Sayaka;Tsuda, Masahiro;Takayama, Kazuo
肝芯片（liver-on-a-chip）是携带肝细胞（例如人类肝细胞）的微流体装置。它用于复制肝脏功能的一部分。许多微流体装置由聚二甲基硅氧烷（PDMS）组成，聚二甲基硅氧烷是一种硅酮弹性体。PDMS易于加工，适用于细胞观察，但其高疏水性存在药物吸收的风险。在这项研究中，我们评估了药物吸收的PDMS设备，并研究了药物的反应性的人肝细胞培养的PDMS设备（肝细胞芯片）。首先，测量12种化合物对PDMS装置的吸收速率。咪达唑仑、丁呋洛尔、环孢素A和维拉帕米的吸收率分别为92.9%、71.7%、71.4%和99.6%，但其他化合物吸收较差。重要的是，化合物的吸收率与其辛醇/水分配系数（log D）值（R-2 = 0.76）相关。接下来，使用肝细胞芯片来检查对药物的反应，这通常用于评估肝功能。利用肝细胞芯片，我们可以确定药物的反应性，包括细胞色素P450（CYP）诱导剂和法尼醇X受体（FXR）配体。我们相信，我们的研究结果将有助于使用基于PDMS的肝脏芯片的药物发现研究。
A liver-on-a-chip (liver-chip) is a microfluidic device carrying liver cells such as human hepatocytes. It is used to reproduce a part of liver function. Many microfluidic devices are composed of polydimethylsiloxane (PDMS), which is a type of silicone elastomer. PDMS is easy to process and suitable for cell observation, but its high hydrophobicity carries the risk of drug absorption. In this study, we evaluated drug absorption to the PDMS device and investigated the drug responsiveness of human hepatocytes cultured in the PDMS device (hepatocyte-chips). First, the absorption rates of 12 compounds to the PDMS device were measured. The absorption rates of midazolam, bufuralol, cyclosporine A, and verapamil were 92.9, 71.7, 71.4, and 99.6%, respectively, but the other compounds were poorly absorbed. Importantly, the absorption rate of the compounds was correlated with their octanol/water distribution coefficient (log D) values (R-2 = 0.76). Next, hepatocyte-chips were used to examine the response to drugs, which are typically used to evaluate hepatic functions. Using the hepatocyte-chips, we could confirm the responsiveness of drugs including cytochrome P450 (CYP) inducers and farnesoid X receptor (FXR) ligands. We believe that our findings will contribute to drug discovery research using PDMS-based liver-chips.