Simulating drug concentrations in PDMS microfluidic organ chips.
Simulating drug concentrations in PDMS microfluidic organ chips.
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DOI：
10.1039/d1lc00348h
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发表时间：
2021-09-14
期刊：
影响因子：
6.1
通讯作者：
Ingber DE
中科院分区：
文献类型：
--
作者：
Grant J;Özkan A;Oh C;Mahajan G;Prantil-Baun R;Ingber DE
微流控器官芯片（Organ Chip）细胞培养装置通常使用聚二甲基硅氧烷（PDMS）制造，因为它具有生物相容性、透明性、弹性和透氧性;然而，疏水性小分子可以吸收到PDMS上，这使得预测药物反应具有挑战性。在这里，我们描述了一个组合的模拟和实验方法来预测的空间和时间的浓度分布的药物下连续给药的PDMS器官芯片含有两个平行的通道，由一个多孔膜，内衬与培养细胞，没有事先知道其log P值。首先，开发了药物损失到芯片中的三维有限元模型，其结合了吸收、吸附、对流和扩散，其模拟药物水平随时间和空间的变化作为潜在PDMS扩散系数和log P值的函数。然后通过实验测量化合物在PDMS中的扩散率，并通过通道流出物中药物浓度的质谱分析确定其分配系数，可以估计化合物的有效log P范围。扩散和分配系数是通过实验推导出的抗疟疾药物和潜在的SARS-CoV-2治疗剂阿莫地喹，并纳入模型中，以定量估计在衬有与肺微血管内皮连接的支气管上皮的人肺气道芯片中测量的随时间推移的药物特异性浓度曲线。相同的策略可以应用于任何装置几何形状、表面处理或体外微流体模型，以在3D中模拟药物的空间和时间梯度，而无需预先知道PDMS中的分配系数或扩散速率。因此，这种方法可以扩展PDMS器官芯片设备用于各种形式的药物测试。
Microfluidic organ-on-a-chip (Organ Chip) cell culture devices are often fabricated using polydimethylsiloxane (PDMS) because it is biocompatible, transparent, elastomeric, and oxygen permeable; however, hydrophobic small molecules can absorb to PDMS, which makes it challenging to predict drug responses. Here, we describe a combined simulation and experimental approach to predict the spatial and temporal concentration profile of a drug under continuous dosing in a PDMS Organ Chip containing two parallel channels separated by a porous membrane that is lined with cultured cells, without prior knowledge of its log P value. First, a three-dimensional finite element model of drug loss into the chip was developed that incorporates absorption, adsorption, convection, and diffusion, which simulates changes in drug levels over time and space as a function of potential PDMS diffusion coefficients and log P values. By then experimentally measuring the diffusivity of the compound in PDMS and determining its partition coefficient through mass spectrometric analysis of the drug concentration in the channel outflow, it is possible to estimate the effective log P range of the compound. The diffusion and partition coefficients were experimentally derived for the antimalarial drug and potential SARS-CoV-2 therapeutic, amodiaquine, and incorporated into the model to quantitatively estimate the drug-specific concentration profile over time measured in human Lung Airway Chips lined with bronchial epithelium interfaced with pulmonary microvascular endothelium. The same strategy can be applied to any device geometry, surface treatment, or in vitro microfluidic model to simulate the spatial and temporal gradient of a drug in 3D without prior knowledge of the partition coefficient or the rate of diffusion in PDMS. Thus, this approach may expand the use of PDMS Organ Chip devices for various forms of drug testing.
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影响因子：
--
作者：
Buchwald P
通讯作者：
Buchwald P
研究肝脏代谢对多器官人体芯片系统中脱靶心脏毒性的影响。
影响因子：
14
作者：
Oleaga C;Riu A;Rothemund S;Lavado A;McAleer CW;Long CJ;Persaud K;Narasimhan NS;Tran M;Roles J;Carmona-Moran CA;Sasserath T;Elbrecht DH;Kumanchik L;Bridges LR;Martin C;Schnepper MT;Ekman G;Jackson M;Wang YI;Note R;Langer J;Teissier S;Hickman JJ
通讯作者：
Hickman JJ
影响因子：
9
作者：
Jalili-Firoozinezhad S;Prantil-Baun R;Jiang A;Potla R;Mammoto T;Weaver JC;Ferrante TC;Kim HJ;Cabral JMS;Levy O;Ingber DE
通讯作者：
Ingber DE
DOI：
10.1016/b978-0-12-813689-8.00015-x
发表时间：
2018-01-01
期刊：
DRUG TARGETING AND STIMULI SENSITIVE DRUG DELIVERY SYSTEMS
影响因子：
--
作者：
Kaur, Gaganjot;Grewal, Jasleen;Madan, Jitender
通讯作者：
Madan, Jitender
影响因子：
3.6
作者：
Lampic, Alina M.;Mackay, Donald;Parnis, J. Mark
通讯作者：
Parnis, J. Mark