A Novel Microfludic Device for Drug Toxicity Studies

Current drug discovery and development efforts are severely limited by expensive animal trials and oversimplified in vitro models. Results obtained from in vitro models are not predictive of in vivo toxicity owing to significant difference from the in vivo physiological conditions. In this context, we propose to develop and demonstrate a novel microfluidic device that reproduces the physiological conditions (morphology, flow and cellular make-up) of organs for quantitative prediction of in vivo toxicity of the drug candidates. While accelerating the drug screening process, this device also offers the promise of reducing animal trials. During Phase I, we demonstrated technology proof-of-principle using liver cells (hepatocytes) as a model for toxicity analysis. Effect of drug permeation, concentration and time dependent toxicity under perfusion and diffusion based conditions was highlighted. Finally, co-culture of vascular and tissue cells mimicking the in vivo conditions were demonstrated. Phase II will expand the platform to include cells from other organs of interest namely brain and kidney. Systems biology approaches will be used to identify biomarkers of toxicity. Whole body concept will be developed to predict metabolized drug induced toxicity on different organs. Finally, framework for a high-throughput drug toxicity assay system will be developed.