Microsensing systems using diamond electrode for <i>in vivo </i>and <i>in vitro</i> detection of drug kinetics
At a Glance
Section titled “At a Glance”| Metadata | Details |
|---|---|
| Publication Date | 2021-01-01 |
| Journal | Proceedings for Annual Meeting of The Japanese Pharmacological Society |
| Authors | Hiroshi Hibino |
| Institutions | The University of Osaka, Pharmac |
| Analysis | Full AI Review Included |
Executive Summary
Section titled “Executive Summary”This research details the development of two novel microsensing systems utilizing advanced diamond electrodes for high-speed, accurate measurement of drug kinetics (in vivo and in vitro).
- Core Value Proposition: Addresses the challenge of obtaining high-speed, accurate drug kinetics data from minimal biological samples or localized in vivo microenvironments, crucial for pharmacology research.
- Material Innovation: The systems leverage diamond electrodes, recognized as a state-of-the-art material for stable and sensitive electrochemistry.
- System 1 (In Vivo): A needle-type diamond electrode integrated with a glass microelectrode allows simultaneous, real-time monitoring of drug concentration and cellular/tissue electrical activities in specific organs of live animals.
- In Vivo Achievement: Successfully measured the pharmacokinetics (PK) and pharmacodynamics (PD) of antiepileptics (lamotrigine) and ototoxic diuretics in the brain and inner ear of rodents.
- System 2 (Ex Vivo): Developed a rapid procedure for quantifying drug concentrations in small biological aliquots.
- Speed and Efficiency: Demonstrated the quantification of the multi-kinase inhibitor pazopanib in a small 100 µL blood sample, completing all processes within 10 minutes.
- Impact: The strategies accelerate drug development timelines and facilitate the implementation of tailored medicine.
Technical Specifications
Section titled “Technical Specifications”| Parameter | Value | Unit | Context |
|---|---|---|---|
| Electrode Material | Diamond | N/A | Chosen for superior electrochemical properties. |
| System 1 Primary Sensor | Needle-type Diamond Electrode | N/A | Used for localized in vivo drug monitoring. |
| System 1 Secondary Sensor | Glass Microelectrode | N/A | Used for detecting cellular/tissue electrical activities. |
| Test Analyte Class 1 | Antiepileptics (Lamotrigine) | N/A | Measured PK/PD in the rodent brain. |
| Test Analyte Class 2 | Loop Diuretic | N/A | Ototoxic compound measured PK/PD in the rodent inner ear. |
| Test Analyte Class 3 | Pazopanib | N/A | Multi-kinase inhibitor quantified ex vivo. |
| Sample Volume (System 2) | ~100 | µL | Required blood sample size for rapid analysis. |
| Total Analysis Time (System 2) | 10 | min | Time required to quantify pazopanib from sample collection. |
| Measurement Environment 1 | In vivo microenvironment | N/A | Localized measurement in organs (e.g., inner ear, brain). |
Key Methodologies
Section titled “Key Methodologies”The research focused on developing and implementing two distinct electrochemical sensing platforms based on diamond electrodes:
- Needle-Type Diamond Electrode Fabrication: Specialized diamond electrodes were engineered into a needle geometry suitable for minimally invasive insertion and localized drug monitoring in live animal organs.
- Integrated In Vivo Platform Assembly: A dual-sensor analytical platform was constructed, pairing the needle-type diamond electrode (for drug concentration measurement) with a glass microelectrode (for simultaneous detection of cellular and tissue electrical activities).
- Real-Time Pharmacokinetic/Pharmacodynamic (PK/PD) Analysis: Systemic administration of test compounds (e.g., lamotrigine) was performed, and the integrated platform measured drug behavior and corresponding electrical signal changes in real time within the target organs of rodents.
- Rapid Ex Vivo Quantification Procedure: A streamlined electrochemical procedure was established to rapidly process and analyze small aliquots of biological fluid, specifically optimized for blood samples (approx. 100 µL).
- High-Throughput Drug Quantification: This rapid procedure was validated by quantifying the multi-kinase inhibitor pazopanib, demonstrating the capability to complete the entire measurement process from sample acquisition to result in 10 minutes.
Commercial Applications
Section titled “Commercial Applications”The developed microsensing technology, leveraging the stability and electrochemical window of diamond electrodes, is highly relevant to several high-value commercial sectors:
- Drug Development and Screening:
- Accelerated PK/PD screening in preclinical models, reducing time and cost associated with traditional methods.
- High-throughput analysis of drug candidates using minimal biological samples.
- Personalized Medicine:
- Rapid Therapeutic Drug Monitoring (TDM) using small blood volumes, enabling quick dose adjustments for critical drugs (e.g., anti-epileptics, chemotherapy agents).
- Advanced Biosensing and Diagnostics:
- Development of highly stable, implantable biosensors for long-term monitoring of biomarkers or drug levels in vivo.
- Neuroscience and Physiology Research:
- Real-time, localized monitoring of neurotransmitter and drug concentrations in the brain and nervous system, coupled with simultaneous electrical activity recording.
- Microelectrode Arrays and Probes:
- Utilization of diamond’s inertness and wide potential window for creating robust microelectrodes suitable for harsh biological or industrial electrochemical environments.
View Original Abstract
High-speed and accurate measurement of drug kinetics in in vivo microenvironment or small aliquot of biological sample is crucial for basic and applied researches in pharmacology. To address this issue is challenging with conventional methods. We developed two different microsensing systems using diamond electrode, a state-of-the-art material for electrochemistry. First technique targets local area of a few organs in live animals. The analytical platform harbors a drug monitoring microsensor composed of needle-type diamond electrode and a glass microelectrode that detects cellular and tissue electrical activities. For test analytes an ototoxic loop diuretic and an antiepileptics lamotrigine were selected; pharmacokinetics and pharmacodynamics of the systemically administrated compounds were measured in real time in the inner ear and brain of rodents, respectively. In each case, the behavior of the drug concentration clearly differed from change of the electrical signals. Second, we described a procedure to rapidly and easily determine drug concentrations in ～100 µL blood sample. With the package of this micro-measurement, we quantified pazopanib, a multi-kinase inhibitor―all the processes were completed in 10 min. The strategies shown here would contribute to advances in drug development and accelerate tailored medicine.