微生理系统(MPS)是用于非临床试验中下一代药物筛选的新兴技术。微生理系统是使用三维体内模拟微环境重建人体器官的生理功能的微流体装置。在未来,MPS有望减少动物实验的数量,改进临床环境中药物疗效的预测方法,并降低药物发现的成本。然而,药物吸附到MPS中使用的聚合物上是评估的关键问题,因为它改变了药物的浓度。聚二甲基硅氧烷(PDMS),用于制造MPS的基本材料,强吸附疏水性药物。作为PDMS的替代品,环烯烃聚合物(COP)已成为低吸附MPS的有吸引力的材料。然而,它很难与不同的材料粘合,因此,并不常用。在这项研究中,我们评估了构成MPS的每种材料的药物吸附特性以及随后的药物毒性变化,以使用COP开发低吸附MPS。疏水性药物环孢菌素A显示出对PDMS的亲和力,并在PDMS-MPS中诱导较低的细胞毒性,但在COP-MPS中没有,而用于粘合的胶带吸附了大量的药物,降低他们的可用性,并且是细胞毒性的。因此,容易吸附的疏水性药物和具有较低细胞毒性的粘合材料应与低吸附聚合物如COP一起使用。
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.