An on-chip small intestine-liver model for pharmacokinetic studies.

Testing of drug effects and cytotoxicity by using cultured cells has been widely performed as an alternative to animal testing. However, the estimation of pharmacokinetics by conventional cell-based assay methods is difficult because of the inability to evaluate multiorgan effects. An important challenge in the field is to mimic the organ-to-organ network in the human body by using a microfluidic network connecting small-scale tissues based on recently emerging MicroTAS (Micro Total Analysis Systems) technology for prediction of pharmacokinetics.

Image-based evaluations of distribution and cytotoxicity of Irinotecan (CPT-11) in a multi-compartment micro-cell coculture device.

We recently developed a polydimethylsiloxane (PDMS)-based three-compartment microfluidic cocultivation device enabling real-time interactions of different cell populations as an advanced physiologically-relevant cell-based assay. This device had valves and small magnetic stirrer-based internal pumps for easy and flexible perfusion operations. In this study, we applied this device for the evaluation of Irinotecan (CPT-11) toxicity to the lung, because it is detoxified by the liver and accumulated in the fat in humans.

Cytotoxicity evaluation of reactive metabolites using rat liver homogenate microsome-encapsulated alginate gel microbeads.

We present an improved cytotoxicity test for reactive metabolites, in which the S9 microsomal fraction of rat liver homogenate is encapsulated in alginate gel microbeads to avoid cytotoxic effects of S9-self-generated toxicants, microsomal lipid peroxides. The S9-encapsulated gel microbeads were prepared by a coaxial two-fluid nozzle and surfaces of the microbeads were coated with poly-L-lysine (PLL). Although the initial metabolic rate of the S9-encapsulated gel microbeads was about 20% slower than that of bare S9, the microbeads prevented the leakage of microsomal lipid peroxides thanks to the dense alginate and PLL polymer networks.

Evaluation of the ecotoxicity of solid wastes using rapid leaching test and bioassays.

A rapid leaching test (RLT) involving the use of ultrasonic irradiation was developed. The applicability and suitability of different leaching procedures for solid wastes were evaluated in terms of the leached concentration of heavy metals and total organic carbon and the ecotoxicity potential of the solid wastes. Solid wastes, including incineration ash and sludge, were used.