Real-Time Measurement of Antiglaucoma Drugs in Porcine Eyes Using Boron-Doped Diamond Microelectrodes
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 fo...
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Published in | ACS sensors Vol. 9; no. 2; pp. 781 - 788 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
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United States
American Chemical Society
23.02.2024
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Subjects | |
Online Access | Get full text |
ISSN | 2379-3694 2379-3694 |
DOI | 10.1021/acssensors.3c02088 |
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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. |
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AbstractList | 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.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. 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. |
Author | Yoneda, Mao Einaga, Yasuaki Ogata, Genki Honjo, Megumi Ogawa, Risa Asai, Kai Yamagishi, Reiko Aihara, Makoto Hanawa, Ai |
AuthorAffiliation | Department of Chemistry Department of Ophthalmology, School of Medicine The University of Tokyo |
AuthorAffiliation_xml | – name: Department of Ophthalmology, School of Medicine – name: Department of Chemistry – name: The University of Tokyo |
Author_xml | – sequence: 1 givenname: Genki orcidid: 0000-0003-1753-428X surname: Ogata fullname: Ogata, Genki organization: Department of Chemistry – sequence: 2 givenname: Mao surname: Yoneda fullname: Yoneda, Mao organization: Department of Chemistry – sequence: 3 givenname: Risa surname: Ogawa fullname: Ogawa, Risa organization: Department of Chemistry – sequence: 4 givenname: Ai surname: Hanawa fullname: Hanawa, Ai organization: Department of Chemistry – sequence: 5 givenname: Kai surname: Asai fullname: Asai, Kai organization: Department of Chemistry – sequence: 6 givenname: Reiko surname: Yamagishi fullname: Yamagishi, Reiko organization: The University of Tokyo – sequence: 7 givenname: Megumi surname: Honjo fullname: Honjo, Megumi organization: The University of Tokyo – sequence: 8 givenname: Makoto surname: Aihara fullname: Aihara, Makoto organization: The University of Tokyo – sequence: 9 givenname: Yasuaki orcidid: 0000-0001-7057-4358 surname: Einaga fullname: Einaga, Yasuaki email: einaga@chem.keio.ac.jp organization: Department of Chemistry |
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Cites_doi | 10.1016/j.diamond.2003.11.082 10.1101/gad.1047403 10.1038/s41551-017-0118-5 10.1016/j.talanta.2014.06.074 10.1111/cts.12448 10.1136/bjo.69.3.217 10.5694/mja2.50020 10.1039/C8AY02197J 10.3390/ph14050480 10.1016/j.heliyon.2023.e15963 10.1126/sciadv.abk2901 10.1016/j.physleta.2009.05.008 10.1021/acs.analchem.0c01707 10.1016/s2589-7500(19)30131-1 10.1126/sciadv.abq4539 10.1001/archopht.1980.01020030543023 10.1016/j.microc.2018.10.042 10.1016/S0140-6736(04)16257-0 10.1016/j.electacta.2018.03.112 10.1109/tbcas.2017.2733624 10.1016/j.ejps.2021.105720 10.1007/978-981-16-7834-9 10.1093/ajhp/62.7.691 10.1089/jop.2019.0102 10.1023/A:1012565026777 10.1021/ac052029x 10.1039/D2AN01037B 10.1126/scitranslmed.3007095 10.1016/j.microc.2018.08.011 |
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Keywords | eye drops pharmacokinetics boron-doped diamond glaucoma drug monitoring |
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Title | Real-Time Measurement of Antiglaucoma Drugs in Porcine Eyes Using Boron-Doped Diamond Microelectrodes |
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