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多器官微器件如何助力药物研发。

How multi-organ microdevices can help foster drug development.

作者信息

Esch Mandy B, Smith Alec S T, Prot Jean-Matthieu, Oleaga Carlota, Hickman James J, Shuler Michael L

机构信息

Department of Biomedical Engineering, Cornell University, 115 and 305 Weill Hall, Ithaca, NY 14853, USA.

NanoScience Technology Center, University of Central Florida, 12424 Research Parkway Suite 401, Orlando, FL 32828, USA.

出版信息

Adv Drug Deliv Rev. 2014 Apr;69-70:158-69. doi: 10.1016/j.addr.2013.12.003. Epub 2014 Jan 9.

Abstract

Multi-organ microdevices can mimic tissue-tissue interactions that occur as a result of metabolite travel from one tissue to other tissues in vitro. These systems are capable of simulating human metabolism, including the conversion of a pro-drug to its effective metabolite as well as its subsequent therapeutic actions and toxic side effects. Since tissue-tissue interactions in the human body can play a significant role in determining the success of new pharmaceuticals, the development and use of multi-organ microdevices present an opportunity to improve the drug development process. The devices have the potential to predict potential toxic side effects with higher accuracy before a drug enters the expensive phase of clinical trials as well as to estimate efficacy and dose response. Multi-organ microdevices also have the potential to aid in the development of new therapeutic strategies by providing a platform for testing in the context of human metabolism (as opposed to animal models). Further, when operated with human biopsy samples, the devices could be a gateway for the development of individualized medicine. Here we review studies in which multi-organ microdevices have been developed and used in a ways that demonstrate how the devices' capabilities can present unique opportunities for the study of drug action. We will also discuss challenges that are inherent in the development of multi-organ microdevices. Among these are how to design the devices, and how to create devices that mimic the human metabolism with high authenticity. Since single organ devices are testing platforms for tissues that can later be combined with other tissues within multi-organ devices, we will also mention single organ devices where appropriate in the discussion.

摘要

多器官微器件能够模拟体外代谢物从一个组织转移到其他组织时发生的组织间相互作用。这些系统能够模拟人体新陈代谢,包括前体药物转化为其有效代谢物以及随后的治疗作用和毒副作用。由于人体中的组织间相互作用在决定新药物的成功与否方面可能起着重要作用,多器官微器件的开发和使用为改进药物开发过程提供了一个契机。这些器件有可能在药物进入昂贵的临床试验阶段之前,更准确地预测潜在的毒副作用,同时估计疗效和剂量反应。多器官微器件还有可能通过提供一个在人体新陈代谢背景下进行测试的平台(与动物模型相对),来辅助新治疗策略的开发。此外,当与人体活检样本一起使用时,这些器件可能成为个性化医疗发展的一个途径。在此,我们回顾了一些研究,其中多器官微器件的开发和使用方式展示了这些器件的能力如何为药物作用研究带来独特的机会。我们还将讨论多器官微器件开发中固有的挑战。其中包括如何设计器件,以及如何创建能够高度逼真地模拟人体新陈代谢的器件。由于单器官器件是用于组织的测试平台,之后可与多器官器件中的其他组织组合,因此在讨论中我们也将酌情提及单器官器件。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f91/4095890/cdc583587ddb/nihms576050f1.jpg

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