Table 2. . Search results on the use of organ-on-a-chips for drug development and toxicity evaluation.
| Study (year) | Type of developed OOAC | Study overview | Ref. |
|---|---|---|---|
| Li et al. (2020) | A 3D human blood-brain barrier chip | The OOAC was used to study the neurotoxicity of INPM. It was shown that the platform effectively mimics the microenvironment and response of the human blood-brain barrier to INPM exposure. An INPM disrupts Keap1-Nrf2-ARE pathways in the blood–brain barrier. | [110] |
| Bovard et al. (2020) | Connected lung/liver-on-a-chip using cocultured normal human bronchial epithelial cells and HepaRG™ liver spheroids | It shows that acute and chronic toxicity of aerosol exposure from aflatoxin B1 (AFB1), as one of anti-tuberculosis agent, was reduced because of the presence of HepaRG™. | [111] |
| Kamei et al. (2017) | Integrated Heart/Cancer on a chip | The OOAC was used to study side effect of Doxorubicin as an anti-cancer drug on human healthy heart cells and liver cancer cells (HepG2) cocultured in a chip. The chip successfully demonstrated how Doxorubicinol, a toxic metabolite from HepG2 cells, is delivered and how it affects the heart cells | [112] |
| Nierode et al. (2016) | A microarray chip platform | The OOAC was used to compare the toxicity of 24 compounds in an undifferentiated and differentiated human neural progenitor cell line. The OOAC platform showed that the acute toxicity of five compounds, acetaminophen, 5-fluorouracil, retinoic acid, Doxorubicin, and pitavastatin, were different from two neural progenitor cell culture conditions. | [113] |
| Kwon et al. (2014) | Transfected enzyme and metabolism chip (Team Chip) | Team Chip was used to predict metabolism-induced drug toxicity or drug-candidate toxicity by manipulating the expression of human metabolizing-enzyme genes using THLE-2 cells and to reveal the specific enzymes related to the drug toxification process. | [114] |
| Jang et al. (2013) | Kidney proximal tubule-on-a-chip with human primary renal tubular cells | The OOAC was used to study nephrotoxicity. It was shown that the toxicity test results were closer to in vivo experiments and proved to be an innovative tool for evaluating human renal toxicity. It was measured by the activity of cisplatin, a proximal tubule nephrotoxin, and P-glycoprotein ATP-binding cassette membrane transporter (Pgp). | [115] |
All investigations prove that OOAC is an excellent approach to studying drugs and toxicity evaluation.
INPM: Indoor nanoscale particulate matter; OOAC: Organ-on-a-chip.