マイクロダイヤモンド電極を用いた皮膚内薬物動態のin vivo計測システムの開発

抄録

Monitoring of plasma drug concentrations is required for effective pharmacotherapy. Repetitive collection of whole blood followed by analysis of plasma samples with conventional methods delays representation of crucial results. Skin is an easily accessible organ; a portion of systemically circulating drug molecules is diffused to the dermal interstitial fluid. Thus, the compound's pharmacokinetics (PK) in the fluid mirrors the plasma PK. To approach such local dermal space, here we describe a microsensing system with a needle-type boron-doped diamond (BDD) electrode, which detects chemical compounds by redox reaction. As a test analyte we chose an anticancer drug, doxorubicin. In an in vitro experiment with a BDD microsensor, doxorubicin elicited a current in response to applied negative potential. Calibration curve covered the therapeutic window (10−100 nM). The sensor's performance was also tested in the collected interstitial fluids. Finally, the sensor was inserted into the dermis layer in anesthetized live rats; after doxorubicin was intravenously injected, the local PK was tracked for >1 hour with the C_max and T_max 3.1 ± 1.4 nM and 33.6 ± 20.6 mins, respectively (n = 7). By combining a formula linking the local measurements to plasma data, this microsensing system may be applicable to real-time monitoring of systemic PK.