关键词: boron-doped diamond drug monitoring eye drops glaucoma pharmacokinetics

Mesh : Swine Animals Humans Antiglaucoma Agents Boron Microelectrodes Chromatography, Liquid Tandem Mass Spectrometry Timolol Glaucoma / drug therapy Diamond

来  源:   DOI:10.1021/acssensors.3c02088

Abstract:
The primary treatment for glaucoma, the most common cause of intermediate vision impairment, involves administering ocular hypotensive drugs in the form of topical eye drops. Observing real-time changes in the drugs that pass through the cornea and reach the anterior chamber of the eye is crucial for improving and developing safe, reliable, and effective medical treatments. Traditional methods for measuring temporal changes in drug concentrations in the aqueous humor employ separation analyzers such as LC-MS/MS. However, this technique requires multiple measurements on the eyes of various test subjects to track changes over time with a high temporal resolution. To address this issue, we have developed a measurement method that employs boron-doped diamond (BDD) microelectrodes to monitor real-time drug concentrations in the anterior chamber of the eye. First, we confirmed the electrochemical reactivity of 13 antiglaucoma drugs in a phosphate buffer solution with a pH of 7.4. Next, we optimized the method for continuous measurement of timolol maleate (TIM), a sympathetic beta-receptor antagonist, and generated calibration curves for each BDD microelectrode using aqueous humor collected from enucleated porcine eyes. We successfully demonstrated the continuous ex vivo monitoring of TIM concentrations in the anterior chambers of these enucleated porcine eyes. The results indicate that changes in intracameral TIM concentrations can be monitored through electrochemical measurements using BDD microelectrodes. This technique holds promise for future advancements in optimizing glaucoma treatment and drug administration strategies.
摘要:
青光眼的主要治疗方法,中间视力障碍最常见的原因,包括以局部滴眼剂的形式施用降眼药物。观察通过角膜并到达眼前房的药物的实时变化对于改善和发展安全性至关重要。可靠,和有效的药物治疗。测量房水中药物浓度随时间变化的传统方法采用分离分析仪,如LC-MS/MS。然而,这种技术需要对各种测试对象的眼睛进行多次测量,以高时间分辨率跟踪随时间的变化。为了解决这个问题,我们开发了一种测量方法,该方法采用掺硼金刚石(BDD)微电极来监测眼睛前房中的实时药物浓度。首先,我们证实了13种抗青光眼药物在pH为7.4的磷酸盐缓冲溶液中的电化学反应性。接下来,我们优化了马来酸噻吗洛尔(TIM)的连续测量方法,一种交感神经β受体拮抗剂,并使用从摘除的猪眼睛收集的房水生成每个BDD微电极的校准曲线。我们成功地证明了这些去核猪眼的前房中TIM浓度的连续离体监测。结果表明,可以通过使用BDD微电极进行电化学测量来监测前房内TIM浓度的变化。该技术有望在优化青光眼治疗和药物施用策略方面取得未来进展。
公众号