| Description | Abstract: Human microphysiological or “Body-on-a-Chip” systems are powerful tools to assess the potential efficacy and toxicity of drugs in pre-clinical studies. Having a human based, multiorgan system, that emulates key aspects of human physiology, can provide important insights to complement animal studies and in vitro studies using human cells from a single organ in the decision about which drugs to move into clinical trials (1). Our human surrogates are constructed using a low cost, robust “pumpless” platform (2). We use this platform in conjunction with “functional” measurements of electrical and mechanical activity of tissue constructs (in collaboration with J. Hickman, University of Central Florida). Also, by combining PBPK-PD models (3) with these devices we can enhance our predictive power for anticipating human responses. Using a system with four or more organs we can predict the exchange of metabolites between organ compartments in response to various drugs and dose levels. Construction of these systems requires materials that reduce unwanted loss of drug and metabolites by absorption to surfaces and the use of a serum-free medium (4). We have constructed models incorporating barrier tissues such as GI tract, blood brain barrier, and skin with internal organs such as liver, cardiac, and neuromuscular junctions, and an immune system mimic (5).With these systems, we can predict both efficacy and toxicity of drugs in humans from preclinical studies (6). Further, we can use these systems to investigate temporal concentration relationships of drugs during preclinical development (7). We believe that these “Body-on-a-Chip” systems have great potential to increase the efficiency of conversion of drug candidates into successful projects.
References:
1.J.H. Sung, et al. 2019. Anal. Chem. 91: 330-351.
2.D.J. LaValley, et al. 2021 Biotechnol. Prog. 37 (2): e3105.
3.J. H. Sung, et al. 2019. APL Bioeng. 3, 021501.
4.Oleaga, C., et al. 2019. Adv. Funct Mater.:1805792
5.T. Sasserath, et al. 2020. Adv. Sci. 7, 2000323.
6.C.W. McAleer, et al. 2019. Sci. Transl. Med. 11: eaav1386.
7.C.W. McAleer, et al. 2019. Sci. Reports 9:9619. |
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