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Placental Drug Transport‐on‐a‐Chip: A Microengineered In Vitro Model of Transporter‐Mediated Drug Efflux in the Human Placental Barrier
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2017-11-09 , DOI: 10.1002/adhm.201700786 Cassidy Blundell 1 , Yoon-Suk Yi 1 , Lin Ma 1 , Emily R Tess 1 , Megan J Farrell 1 , Andrei Georgescu 1 , Lauren M Aleksunes 2 , Dongeun Huh 1
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2017-11-09 , DOI: 10.1002/adhm.201700786 Cassidy Blundell 1 , Yoon-Suk Yi 1 , Lin Ma 1 , Emily R Tess 1 , Megan J Farrell 1 , Andrei Georgescu 1 , Lauren M Aleksunes 2 , Dongeun Huh 1
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The current lack of knowledge about the effect of maternally administered drugs on the developing fetus is a major public health concern worldwide. The first critical step toward predicting the safety of medications in pregnancy is to screen drug compounds for their ability to cross the placenta. However, this type of preclinical study has been hampered by the limited capacity of existing in vitro and ex vivo models to mimic physiological drug transport across the maternal–fetal interface in the human placenta. Here the proof‐of‐principle for utilizing a microengineered model of the human placental barrier to simulate and investigate drug transfer from the maternal to the fetal circulation is demonstrated. Using the gestational diabetes drug glyburide as a model compound, it is shown that the microphysiological system is capable of reconstituting efflux transporter‐mediated active transport function of the human placental barrier to limit fetal exposure to maternally administered drugs. The data provide evidence that the placenta‐on‐a‐chip may serve as a new screening platform to enable more accurate prediction of drug transport in the human placenta.
中文翻译：
胎盘药物芯片转运：人胎盘屏障中转运蛋白介导的药物流出的微工程体外模型
目前缺乏关于母体用药对发育中胎儿的影响的了解，这是全世界主要的公共卫生问题。预测妊娠期药物安全性的第一个关键步骤是筛选药物化合物穿过胎盘的能力。然而，这种类型的临床前研究受到现有体外和离体模型模拟人胎盘中母胎界面生理药物转运能力有限的阻碍。这里展示了利用人类胎盘屏障的微工程模型来模拟和研究药物从母体到胎儿循环的转移的原理验证。使用妊娠糖尿病药物格列本脲作为模型化合物，表明微生理系统能够重建人胎盘屏障的外排转运蛋白介导的主动转运功能，以限制胎儿接触母体给药的药物。这些数据提供证据表明胎盘芯片可以作为新的筛选平台，以更准确地预测人类胎盘中的药物转运。
更新日期：2017-11-09
中文翻译：
胎盘药物芯片转运：人胎盘屏障中转运蛋白介导的药物流出的微工程体外模型
目前缺乏关于母体用药对发育中胎儿的影响的了解，这是全世界主要的公共卫生问题。预测妊娠期药物安全性的第一个关键步骤是筛选药物化合物穿过胎盘的能力。然而，这种类型的临床前研究受到现有体外和离体模型模拟人胎盘中母胎界面生理药物转运能力有限的阻碍。这里展示了利用人类胎盘屏障的微工程模型来模拟和研究药物从母体到胎儿循环的转移的原理验证。使用妊娠糖尿病药物格列本脲作为模型化合物，表明微生理系统能够重建人胎盘屏障的外排转运蛋白介导的主动转运功能，以限制胎儿接触母体给药的药物。这些数据提供证据表明胎盘芯片可以作为新的筛选平台，以更准确地预测人类胎盘中的药物转运。
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