Relationship between Adsorption and Toxicity of Nephrotoxic Drugs in Microphysiological Systems (MPS)

Abstract

Microphysiological systems (MPS) are an emerging technology for next-generation drug screening in non-clinical tests. Microphysiological systems are microfluidic devices that reconstitute the physiological functions of a human organ using a three-dimensional in vivo-mimicking microenvironment. In the future, MPSs are expected to reduce the number of animal experiments, improve prediction methods for drug efficacy in clinical settings, and reduce the costs of drug discovery. However, drug adsorption onto the polymers used in an MPS is a critical issue for assessment because it changes the concentration of the drug. Polydimethylsiloxane (PDMS), a basic material used for the fabrication of MPS, strongly adsorbs hydrophobic drugs. As a substitute for PDMS, cyclo-olefin polymer (COP) has emerged as an attractive material for low-adsorption MPS. However, it has difficulty bonding with different materials and, therefore, is not commonly used. In this study, we assessed the drug adsorption properties of each material constituting an MPS and subsequent changes in drug toxicity for the development of a low-adsorption MPSs using COP. The hydrophobic drug cyclosporine A showed an affinity for PDMS and induced lower cytotoxicity in PDMS-MPS but not in COP-MPS, whereas adhesive tapes used for bonding adsorbed a significant quantity of drugs, lowering their availability, and was cytotoxic. Therefore, easily-adsorbed hydrophobic drugs and bonding materials having lower cytotoxicity should be used with a low-adsorption polymer such as COP.

Keywords

• microphysiological system (MPS)
• cyclo-olefin polymer (COP)
• nephrotoxicity
• drug adsorption
• drug screening