The role of body-on-a-chip devices in drug and toxicity studies.

摘要

High-quality, in vitro screening tools are essential in identifying promising compounds during drug development. Tests with currently used cell-based assays provide an indication of a compound's potential therapeutic benefits to the target tissue, but not to the whole body. Data obtained with animal models often cannot be extrapolated to humans. Multicompartment microfluidic-based devices, particularly those that are physical representations of physiologically based pharmacokinetic (PBPK) models, may contribute to improving the drug development process. These scaled-down devices, termed micro cell culture analogs (muCCAs) or body-on-a-chip devices, can simulate multitissue interactions under near-physiological fluid flow conditions and with realistic tissue-to-tissue size ratios. Because the device can be used with both animal and human cells, it can facilitate cross-species extrapolation. Used in conjunction with PBPK models, the devices permit an estimation of effective concentrations that can be used for studies with animal models or predict the human response. The devices also provide a means for relatively high-throughput screening of drug combinations and, when utilized with a patient's tissue sample, an opportunity for individualized medicine. Here we review efforts made toward the development of microfabricated cell culture systems and give examples that demonstrate their potential use in drug development, such as identifying synergistic drug interactions as well as simulating multiorgan metabolic interactions. In addition to their use in drug development, the devices also can be used to estimate the toxicity of chemicals as occupational hazards and environmental contaminants.