Abstract：
Antihistamines relieve allergic symptoms by inhibiting the action of histamine. Further understanding of antihistamine transmembrane mechanisms and optimizing the selectivity and real-time monitoring capabilities of drug sensors is necessary. In this study, a micrometer liquid/liquid (L/L) interfacial sensor has served as a biomimetic membrane to investigate the mechanism of interfacial transfer of five antihistamines, i.e., clemastine (CLE), cyproheptadine (CYP), epinastine (EPI), desloratadine (DSL), and cetirizine (CET), and realize the real-time determinations. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) techniques have been used to uncover the electrochemical transfer behavior of the five antihistamines at the L/L interface. Additionally, finite element simulations (FEMs) have been employed to reveal the thermodynamics and kinetics of the process. Visualization of antihistamine partitioning in two phases at different pH values can be realized by ion partition diagrams (IPDs). The IPDs also reveal the transfer mechanism at the L/L interface and provide effective lipophilicity at different pH values. Real-time determinations of these antihistamines have been achieved through potentiostatic chronoamperometry (I-t), exhibiting good selectivity with the addition of nine common organic or inorganic compounds in living organisms and revealing the potential for in vivo pharmacokinetics. Besides providing a satisfactory surrogate for studying the transmembrane mechanism of antihistamines, this work also sheds light on micro- and nano L/L interfacial sensors for in vivo analysis of pharmacokinetics at a single-cell or single-organelle level.
摘要：
抗组胺药通过抑制组胺的作用来缓解过敏症状。有必要进一步了解抗组胺跨膜机制并优化药物传感器的选择性和实时监测能力。在这项研究中,微米液体/液体（L/L）界面传感器已用作仿生膜，以研究五种抗组胺药的界面转移机理，即，氯马斯汀（CLE），赛庚啶（CYP），epinastine（EPI），地氯雷他定（DSL），和西替利嗪（CET），并实现实时判断。循环伏安法（CV）和差分脉冲伏安法（DPV）技术已用于揭示五种抗组胺药在L/L界面的电化学转移行为。此外,有限元模拟(FEM)已被用来揭示过程的热力学和动力学。可以通过离子分区图（IPD）实现在不同pH值下在两个阶段中分配抗组胺药的可视化。IPD还揭示了L/L界面处的转移机制，并在不同pH值下提供了有效的亲脂性。这些抗组胺药的实时测定是通过恒电位计时电流法（I-t）实现的，在生物体中添加九种常见的有机或无机化合物，表现出良好的选择性，并揭示了体内药代动力学的潜力。除了为研究抗组胺药的跨膜机制提供令人满意的替代外，这项工作也为在单细胞或单细胞器水平进行体内药代动力学分析的微米和纳米L/L界面传感器提供了启示。
