An openable artificial intestinal tract system for the in vitro evaluation of medicines

Abstract

AbstractIn vitro drug screening systems for pharmacological targets have been studied as substitutes for whole-animal experiments. Cultured cells or tissues provide promising substitution models when coupled with technological innovations in micro total analysis systems. In this study, we focus on an intestinal drug absorption assay, as the oral route is most frequently used for drug administration. Pharmacological studies have reported the development of artificial vessels that include tubular structures. However, it is difficult to observe the insides of these tubes in situ. To address this problem, we developed a micro-device that uses a pneumatic balloon actuator (PBA) to open and close an artificial intestinal tract. A human colon carcinoma cell line (Caco-2) was cultivated on the flat surface of the micro-device for 7 days to form the inner cellular layer of an artificial intestinal tract with which to evaluate drug transport. The artificial intestinal tract was completely actuated from a flat plate to a circular tube via a PBA with a pressure of 65 kPa, and drugs were perfused at a flow rate of 0.05 mL min−1 into the tubular artificial intestinal tract for 1 h. Using the openable artificial intestinal tract, the in vitro absorption of calcein and Texas Red were successfully estimated as models of hydrophilic and hydrophobic drugs, respectively. The artificial intestinal tract enables the effective evaluation of the in vitro intestinal absorption of drug candidates and contributes to the reduction of costs incurred during the initial stage of drug development.