Drug permeability assay using microhole-trapped cells in a microfluidic device.

As orally administered drugs must be absorbed from the intestine into the blood circulation, permeability assays of drug candidates have been widely used in the early screening stages of drug discovery. In this study, a microfluidic device was developed for the drug permeability assay, considering the in vivo delivery path of drugs in humans. A microhole array for cell trapping was fabricated using the poly(dimethylsiloxane) (PDMS) molding technique by mimicking the intestinal epithelial cell membrane. On the basis of mathematical simulations, the configuration of the microfluidic device, including a microhole array and a mixing channel, was optimized to trap cells firmly in each microhole. At the flow rate under optimal conditions, cells were effectively trapped in a microhole array without cell damage. We measured the permeability of 10 drugs, including those with high and low permeability in microchannels, and compared the results with the reported values of permeability in the human and rat intestine. Most drugs had a high p value (p > 0.4), and only a few drugs had a low p value less than 0.05 by t test. Though their measured permeabilities are not the same as those in vivo human intestine, it shows that in vivo permeabilities in the human and rat intestine are highly correlated with those measured by the microfluidic device (R(2) = 0.9013 and R(2) = 0.8765, respectively). Also, the fraction of the dose absorbed in the human intestine (F(a)) indicated that the drug permeability measured using this device was significantly correlated (R(2) = 0.9641) with those in human subjects. As the microfluidic assay system is dependent on cells trapped inside a microhole array, it is a valuable tool in drug discovery as well as an alternative to animal testing.