Microphysiological heart-liver body-on-a-chip system with a skin mimic for evaluating topical drug delivery
Microphysiological heart-liver body-on-a-chip system with a skin mimic for evaluating topical drug delivery
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DOI：
10.1039/c9lc00861f
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发表时间：
2020-02-21
期刊：
影响因子：
6.1
通讯作者：
Hickman, James J.
中科院分区：
文献类型：
--
作者：
de Mello, Camilly P. Fires;Carmona-Moran, Carlos;Hickman, James J.
体外芯片上的身体系统是一种很有前途的技术，其目的是与传统的动物模型相比，提高对人类药物疗效和毒性的预测能力。在这里，我们开发了一种新的心脏-肝脏芯片上的身体系统，该系统具有皮肤替代物，以评估局部给药药物的毒性。为了测试该系统的效用，通过合成皮肤替代物（Strat-M膜）局部应用双氯芬酸、酮康唑、氢化可的松和对乙酰氨基酚，并将毒性结果与全身应用化合物的急性药物暴露结果进行比较。心脏-肝脏系统成功预测了化合物对心脏和肝脏功能变化的影响。与全身相比，局部应用的药物浓度的差异表明皮肤替代物的屏障性质是有效的。该心脏-肝脏系统的一个重要优势是能够显示急性和慢性药物暴露的不同影响，这是人用药品注册技术要求国际协调会（ICH）三部分指导原则的一部分。总之，这项工作表明了一个有前途的心脏-肝脏芯片上的身体系统，可用于评估皮肤吸收的潜在药物毒性，以及评估通过皮肤在同一系统中的运输动力学。
Body-on-a-chip in vitro systems are a promising technology that aims to increase the predictive power of drug efficacy and toxicity in humans when compared to traditional animal models. Here, we developed a new heart-liver body-on-a-chip system with a skin surrogate to assess the toxicity of drugs that are topically administered. In order to test the utility of the system, diclofenac, ketoconazole, hydrocortisone and acetaminophen were applied topically through a synthetic skin surrogate (Strat-M membrane) and the toxicity results were compared to those of acute drug exposure from systemically applying the compounds. The heart-liver system was successful in predicting the effects for both cardiac and liver functions changes due to the compounds. The difference in the concentrations of drugs applied topically compared to systemically indicates that the barrier properties of the skin surrogate were efficient. One important advantage of this heart-liver system was the capability of showing differential effects of acute and chronic drug exposure which is necessary as part of the International Conference in Harmonisation (ICH) tri-partate guidelines. In conclusion, this work indicates a promising heart-liver body-on-a-chip system that can be used for the assessment of potential drug toxicity from dermal absorption as well as evaluate transport dynamics through the skin in the same system.