Characterization of drug metabolites and cytotoxicity assay simultaneously using an integrated microfluidic device
Characterization of drug metabolites and cytotoxicity assay simultaneously using an integrated microfluidic device
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使用集成微流体装置同时表征药物代谢物和细胞毒性测定
DOI：
10.1039/b809117j
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发表时间：
2009-01-01
期刊：
影响因子：
6.1
通讯作者：
Lin, Bingcheng
中科院分区：
文献类型：
--
作者：
Ma, Bo;Zhang, Guohao;Lin, Bingcheng
开发了一种集成微流体装置，用于同时表征药物代谢物和细胞毒性测定。该多层器件由嵌入分离微通道的石英衬底、含人肝微粒体（HLM）溶胶-凝胶生物反应器的穿孔三微孔阵列和两层PDMS组成。通过将石英衬底上的微孔阵列与底部PDMS层的细胞培养室对齐，将与功能单元相关的药物代谢研究，包括代谢物的产生、检测和培养细胞的孵育，以评估代谢诱导的细胞毒性，都整合到微流控装置中。为了验证在微流控芯片上进行药物代谢研究的可行性，我们首先研究了对乙酰氨基酚（AP）的udp -葡萄糖醛酸糖基转移酶（UGT）代谢及其对hepG2细胞毒性的影响。然后在该装置上证明了AP与苯妥英（PH）之间基于代谢的药物-药物相互作用，导致hepG2细胞毒性增加。这些都表明，所开发的微流体装置可能是药物代谢和基于代谢的药物相互作用研究的潜在有用工具。
An integrated microfluidic device was developed for the characterization of drug metabolites and a cytotoxicity assay simultaneously. The multi-layer device was composed of a quartz substrate with embedded separation microchannels and a perforated three-microwell array containing sol-gel bioreactors of human liver microsome (HLM), and two PDMS layers. By aligning the microwell array on the quartz substrate with cell culture chambers on the bottom PDMS layer, drug metabolism studies related to functional units, including metabolite generation, detection and incubation with cultured cells to assess metabolism induced cytotoxicity, were all integrated into the microfluidic device. To validate the feasibility of drug metabolism study on the microfluidic chip, UDP-glucuronosyltransferase (UGT) metabolism of acetaminophen (AP) and its effect on hepG2 cytotoxicity were studied first. Then metabolism based drug-drug interaction between AP and phenytoin (PH), which resulted in increased hepG2 cytotoxicity, was proved on this device. All this demonstrated that the developed microfluidic device could be a potential useful tool for drug metabolism and metabolism based drug-drug interaction research.