TY - JOUR
T1 - A microsensing system for the in vivo real-time detection of local drug kinetics
AU - Ogata, Genki
AU - Ishii, Yuya
AU - Asai, Kai
AU - Sano, Yamato
AU - Nin, Fumiaki
AU - Yoshida, Takamasa
AU - Higuchi, Taiga
AU - Sawamura, Seishiro
AU - Ota, Takeru
AU - Hori, Karin
AU - Maeda, Kazuya
AU - Komune, Shizuo
AU - Doi, Katsumi
AU - Takai, Madoka
AU - Findlay, Ian
AU - Kusuhara, Hiroyuki
AU - Einaga, Yasuaki
AU - Hibino, Hiroshi
N1 - Funding Information:
We thank P. Bredeloux for comments on the experimental results, and Y. Takahashi and H. Shiku for technical advice. This study was partially supported by the following research grants: Grant-in-Aid for Scientific Research B 25293058 (to H.H.); Grant-in-Aid for Scientific Research C 15K10770 (to K.D.); and Grants-in-Aid for Young Scientists B 25870248 (to F.N.) and 26870210 (to G.O.) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and JST-ACCEL (to Y.E.). In addition, funds were provided by the Nakatani Foundation (to H.H.), Takeda Science Foundation (to F.N.), Uehara Memorial Foundation (to F.N.) and Astellas Foundation for Research on Metabolic Disorders (to F.N.).
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/8/1
Y1 - 2017/8/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41551-017-0118-5
DO - 10.1038/s41551-017-0118-5
M3 - Article
AN - SCOPUS:85031909673
SN - 2157-846X
VL - 1
SP - 654
EP - 666
JO - Nature Biomedical Engineering
JF - Nature Biomedical Engineering
IS - 8
ER -