Ogata Genki, Ishii Yuya, Asai Kai, Sano Yamato, Nin Fumiaki, Yoshida Takamasa, Higuchi Taiga, Sawamura Seishiro, Ota Takeru, Hori Karin, Maeda Kazuya, Komune Shizuo, Doi Katsumi, Takai Madoka, Findlay Ian, Kusuhara Hiroyuki, Einaga Yasuaki, Hibino Hiroshi
Department of Molecular Physiology, Niigata University School of Medicine, Niigata, 951-8510, Japan.
Center for Transdisciplinary Research, Niigata University, Niigata, 950-2181, Japan.
Nat Biomed Eng. 2017 Aug;1(8):654-666. doi: 10.1038/s41551-017-0118-5. Epub 2017 Aug 9.
Real-time recording of the kinetics of systemically administered drugs in in vivo microenvironments may accelerate the development of effective medical therapies. However, conventional methods require considerable analyte quantities, have low sampling rates and do not address how drug kinetics correlate with target function over time. Here, we describe the development and application of a drug-sensing system consisting of a glass microelectrode and a microsensor composed of boron-doped diamond with a tip of around 40 μm in diameter. We show that, in the guinea pig cochlea, the system can measure-simultaneously and in real time-changes in the concentration of bumetanide (a diuretic that is ototoxic but applicable to epilepsy treatment) and the endocochlear potential underlying hearing. In the rat brain, we tracked the kinetics of the drug and the local field potentials representing neuronal activity. We also show that the actions of the antiepileptic drug lamotrigine and the anticancer reagent doxorubicin can be monitored in vivo. Our microsensing system offers the potential to detect pharmacological and physiological responses that might otherwise remain undetected.
在体内微环境中对全身给药药物的动力学进行实时记录，可能会加速有效药物治疗方法的开发。然而，传统方法需要大量的分析物，采样率低，并且没有解决药物动力学如何随时间与靶标功能相关联的问题。在此，我们描述了一种药物传感系统的开发和应用，该系统由玻璃微电极和一个微传感器组成，该微传感器由硼掺杂金刚石制成，尖端直径约为40μm。我们表明，在豚鼠耳蜗中，该系统可以同时实时测量布美他尼（一种具有耳毒性但可用于癫痫治疗的利尿剂）的浓度变化以及听力所依赖的内耳蜗电位。在大鼠大脑中，我们追踪了药物的动力学以及代表神经元活动的局部场电位。我们还表明，可以在体内监测抗癫痫药物拉莫三嗪和抗癌试剂阿霉素的作用。我们的微传感系统具有检测其他情况下可能无法检测到的药理和生理反应的潜力。
