Real-time intraocular antiglaucoma drugs measurement in porcine eyes using boron-doped diamond microelectrodes.
At a Glance
Section titled “At a Glance”| Metadata | Details |
|---|---|
| Publication Date | 2023-01-01 |
| Journal | Proceedings for Annual Meeting of The Japanese Pharmacological Society |
| Authors | Genki Ogata, Mao Yoneda, Risa Ogawa, Ai Hanawa, Kai Asai |
| Institutions | Keio University, The University of Tokyo |
| Analysis | Full AI Review Included |
Executive Summary
Section titled “Executive Summary”This research details the development and application of Boron-Doped Diamond (BDD) microelectrodes for continuous, real-time monitoring of antiglaucoma drug concentrations in ocular tissue.
- Core Value Proposition: Addresses the critical need for high temporal resolution pharmacokinetic data regarding ocular hypotensive drugs (e.g., Timolol maleate, TIM) reaching the anterior chamber.
- Technological Solution: Utilizes highly stable Boron-Doped Diamond (BDD) microelectrodes as electrochemical sensors, overcoming the limitations of conventional sampling methods.
- Limitation Addressed: Conventional methods (e.g., LC-MS/MS) require multiple measurements across multiple test subjects, resulting in poor temporal resolution for tracking drug dynamics in a single eye.
- Target Application: Monitoring the penetration and concentration of Timolol maleate (TIM), a sympathetic beta-receptor antagonist used in glaucoma treatment.
- Key Achievement: Successful optimization and demonstration of continuous ex vivo monitoring of TIM concentration changes within the aqueous humor of enucleated porcine eyes.
- Conclusion: BDD microelectrodes are a viable, reliable platform for real-time intracameral drug concentration monitoring, facilitating the development of safer and more effective ophthalmic treatments.
Technical Specifications
Section titled “Technical Specifications”The following table summarizes the key technical parameters and context derived from the study abstract.
| Parameter | Value | Unit | Context |
|---|---|---|---|
| Sensor Material | Boron-Doped Diamond (BDD) | N/A | Used for high-performance electrochemical sensing |
| Sensor Geometry | Microelectrode | N/A | Designed for minimally invasive intraocular measurement |
| Target Analyte | Timolol maleate (TIM) | N/A | Sympathetic beta-receptor antagonist (Antiglaucoma drug) |
| Measurement Mode | Continuous | N/A | Enables real-time tracking of temporal changes |
| Measurement Location | Anterior Chamber | N/A | Monitoring drug concentration in the aqueous humor |
| Biological Model | Porcine eyes | N/A | Used for ex vivo demonstration and calibration |
| Calibration Matrix | Aqueous Humor | N/A | Fluid collected from porcine eyes for sensor calibration |
| Resolution Goal | High | Temporal | Required for observing rapid drug changes post-administration |
| Conventional Method | LC-MS/MS | N/A | Benchmark method lacking sufficient temporal resolution |
Key Methodologies
Section titled “Key Methodologies”The experimental approach focused on validating the BDD microelectrode platform for continuous drug monitoring in a relevant biological model.
- System Development: A novel measurement method was developed utilizing boron-doped diamond (BDD) microelectrodes specifically designed to track drug concentrations.
- Analyte Selection: Timolol maleate (TIM), a common antiglaucoma drug, was selected as the target analyte for continuous measurement.
- Method Optimization: The electrochemical method was optimized to ensure continuous and reliable measurement of TIM.
- Calibration: Calibration curves for individual BDD microelectrodes were obtained using aqueous humor collected from porcine eyes to ensure accuracy in the biological matrix.
- Ex Vivo Demonstration: Continuous ex vivo monitoring of TIM concentration was performed by inserting the BDD microelectrodes into the anterior chamber of enucleated porcine eyes.
- Validation: The results confirmed that changes in intracameral TIM concentration could be successfully monitored in real-time using the BDD microelectrodes.
Commercial Applications
Section titled “Commercial Applications”The use of BDD microelectrodes for real-time drug monitoring has significant implications across several high-tech and biomedical sectors, leveraging the material’s stability, wide potential window, and biocompatibility.
- Ophthalmology and Drug Delivery:
- Real-time pharmacokinetic studies for topical eye drops.
- Optimization of drug formulation and dosing schedules for glaucoma and other ocular diseases.
- Development of personalized medicine approaches based on individual drug absorption rates.
- Biomedical and Implantable Sensors:
- Creation of stable, long-term implantable sensors for monitoring drug levels or biomarkers in vivo.
- Minimally invasive diagnostic tools for complex biological fluids.
- Pharmaceutical Research and Development (R&D):
- High-throughput screening of drug candidates and delivery systems in preclinical models.
- Accelerated testing of transdermal or transmucosal drug absorption efficiency.
- Advanced Electrochemistry:
- Use of BDD electrodes in harsh or complex matrices where conventional electrodes fail due to fouling or corrosion.
- Development of highly sensitive detectors for liquid chromatography (LC) systems, potentially replacing or augmenting LC-MS/MS in certain applications requiring high temporal resolution.
View Original Abstract
The primary treatment for glaucoma, the leading cause of intermediate vision impairment, involves administering ocular hypotensive drugs in topical eye drops. Observation of the real-time changes in the drugs through the cornea and reaching the anterior chamber is essential to improve or develop a safe, reliable, and effective medical treatment. Conventional methods such as LC-MS/MS are used to measure the temporal changes in the drug in the aqueous humor; however, this technique involves multiple measurements of the eyes of multiple test subjects to measure changes over time with high temporal resolution. To resolve this problem, we develop a measurement method that utilizes boron-doped diamond (BDD) microelectrodes to track the real-time drug concentrations in the anterior chamber of the eye. First, we optimize the method for continuously measuring timolol maleate (TIM), a sympathetic beta-receptor antagonist, and obtain the calibration curves of each BDD microelectrode in the aqueous humor collected from porcine eyes. Next, we demonstrate the continuous ex vivo monitoring of the TIM in the enucleated porcine eyes. The results suggest that changes in the intracameral TIM concentration can be monitored using BDD microelectrodes.