Ogawa Risa, Ogata Genki, Yamagishi Reiko, Honjo Megumi, Aihara Makoto, Einaga Yasuaki
Department of Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Yokohama 223-8522, Japan.
Department of Ophthalmology, School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan.
ACS Sens. 2025 Jun 27;10(6):4145-4152. doi: 10.1021/acssensors.5c00220. Epub 2025 Apr 7.
The corneal permeability of an eye drop is crucial in drug delivery into the eye, but our understanding of drug migration through the cornea and drug distribution within the anterior chamber still requires improvement. To this end, we developed an electrochemical method using boron-doped diamond (BDD) to monitor real-time changes in the drug concentration in the anterior chamber. A needle-shaped BDD microelectrode, with a respective length and tip diameter of ∼200 and ∼40 μm, was used in the in vivo detection of brimonidine tartrate (BRM), which is a widely used antiglaucoma drug. We inserted the tip of the electrode into the right cornea of an anesthetized mouse. BRM was then administered to the right eye, resulting in the successful real-time monitoring of the changes in current. The recorded current reflected the combined reduction of BRM and dissolved oxygen within the anterior chamber. Based on the subtraction of the contribution of the oxygen, the BRM-specific reduction current increased immediately after administration, corresponding to 4.1 μM. Validation via liquid chromatography-tandem mass spectrometry confirmed the accuracy of this approach. Notably, the pharmacological effect of BRM, i.e., a reduced intraocular pressure, was observed 30 min after administration, lagging behind drug migration. These findings may provide valuable insights into the ocular pharmacokinetics of novel drugs and facilitate the development of more effective therapeutic approaches.
眼药水的角膜通透性在药物输送到眼内的过程中至关重要，但我们对药物透过角膜的迁移以及在前房内的药物分布的理解仍有待提高。为此，我们开发了一种使用硼掺杂金刚石（BDD）的电化学方法，以监测前房内药物浓度的实时变化。使用了一种针状BDD微电极，其长度和尖端直径分别约为200和40μm，用于体内检测酒石酸溴莫尼定（BRM），这是一种广泛使用的抗青光眼药物。我们将电极尖端插入麻醉小鼠的右角膜。然后将BRM滴入右眼，成功实时监测电流变化。记录的电流反映了前房内BRM和溶解氧的综合减少。基于对氧贡献的扣除，给药后BRM特异性还原电流立即增加，相当于4.1μM。通过液相色谱-串联质谱法进行的验证证实了该方法的准确性。值得注意的是，给药30分钟后观察到BRM的药理作用，即眼压降低，这滞后于药物迁移。这些发现可能为新型药物的眼内药代动力学提供有价值的见解，并促进更有效治疗方法的开发。
