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α-环糊精对药物分布的影响——通过不相溶电解质溶液界面的电化学方法进行研究

Effect of alpha-cyclodextrin on drug distribution studied by electrochemistry at interfaces between immiscible electrolyte solutions.

作者信息

Deryabina Maria A, Hansen Steen H, Østergaard Jesper, Jensen Henrik

机构信息

Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.

出版信息

J Phys Chem B. 2009 May 21;113(20):7263-9. doi: 10.1021/jp901247p.

Abstract

The description and understanding of noncovalent interactions and distribution of potential new drug compounds in an organism is of paramount importance for the successful development of new drugs. In this work, a new procedure based on electrochemistry at the interface between two immiscible electrolyte solutions (ITIES) for addressing and discriminating between drug compound/ligand interactions in aqueous solution and nonspecific ligand effects on oil-water distribution behavior has been developed. The procedure is demonstrated using five drug compounds with different physical chemical parameters and alpha-cyclodextrin as the aqueous phase ligand. Alpha-cyclodextrin was chosen as an aqueous phase ligand, as it is frequently used in drug formulations to enhance solubility and bioavailability of drug compounds. Supplementary capillary electrophoresis experiments provided more detailed information on alpha-cyclodextrin drug complexation and, in combination with the electrochemical studies, provided information on solvation effects affecting the oil-water distribution of the drug compounds. The use of ligand shift ion partition diagrams for data presentation is a convenient format for the visualization of ligand effects on distribution behavior of related drug compounds.

摘要

对于新型药物的成功研发而言,描述和理解非共价相互作用以及潜在新药化合物在生物体内的分布至关重要。在这项工作中,已开发出一种基于两种不混溶电解质溶液(ITIES)界面处电化学的新方法,用于研究和区分水溶液中药物化合物/配体相互作用以及非特异性配体对油水分配行为的影响。使用具有不同物理化学参数的五种药物化合物和α-环糊精作为水相配体对该方法进行了验证。选择α-环糊精作为水相配体,是因为它常用于药物制剂中以提高药物化合物的溶解度和生物利用度。补充毛细管电泳实验提供了有关α-环糊精与药物络合的更详细信息,并且与电化学研究相结合,提供了影响药物化合物油水分配的溶剂化效应信息。使用配体转移离子分配图来呈现数据是一种方便的形式,可用于直观展示配体对相关药物化合物分布行为的影响。

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