The authors present a microfluidic device to expose cancer cells to a dynamic, in vivo-like concentration profile of a drug and quantify its efficacy on-chip. In conventional cell culture experiments drug efficacy is tested under static concentrations, whereas in vivo drug concentration follows a pharmacokinetic profile with an initial peak and a decline over time. With the rise of microfluidic cell culture models, including organs-on-chips, there are opportunities to more realistically mimic in vivo-like concentrations. In this study, the microfluidic device contains a cell culture chamber and a drug-dosing channel separated by a transparent membrane, to allow for shear stress-free drug exposure and label-free growth quantification. Dynamic drug concentration profiles in the cell culture chamber were controlled by continuously keeping controlled concentrations of the drug in the dosing channel. The control over drug concentrations in the cell culture chambers was validated with fluorescence experiments and numerical simulations. Exposure of HCT116 colorectal cancer cells to static concentrations of the clinically used drug oxaliplatin resulted in a sensible dose-effect curve. Dynamic, in vivo-like drug exposure also led to statistically significant lower growth compared to untreated control. Continuous exposure to the average concentration of the in vivo-like exposure seems more effective than exposure to the peak concentration only. This microfluidic system will improve efficacy prediction of in vitro models, including organs-on-chips, and may lead to future clinical optimization of drug administration schedules.
Controlled pharmacokinetic anti-cancer drug concentration profiles lead to growth inhibition of colorectal cancer cells in a microfluidic device
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