Study of penetration mechanism of labrasol on rabbit cornea by Ussing chamber, RT-PCR assay, Western blot and immunohistochemistry

作     者：Pan Guo Nan Li Lili Fan Jun Lu Boying Liu Bing Zhang Yumei Wu Zhidong Liu Jiawei Li Jiaxin Pi Dongli Qi 

作者机构：Tianjin State Key Laboratory of Modern Chinese MedicineThe Institute of Traditional Chinese MedicineTianjinUniversity of Traditional Chinese MedicineNo.88Yuquan RoadTianjin300193China Engineering Research Center of Modern Chinese Medicine Discovery and PreparationTianjin University ofTraditional Chinese MedicineNo.88Yuquan RoadTianjin300193China School of Pharmaceutical Science and TechnologyTianjin UniversityTianjin300193China 

出 版 物：《Asian Journal of Pharmaceutical Sciences》 (亚洲药物制剂科学（英文）)

年 卷 期：2019年第14卷第3期

页      面：329-339页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 1002[医学-临床医学] 10[医学] 100602[医学-中西医结合临床] 

主　　题：Enhanced corneal permeation Tight junctions associated proteins Labrasol Ussing chamber Western blot Immunohistochemistry 

摘      要：Labrasol, as a non-ionic surfactant, can enhance the permeation and absorption of drugs, and is extensively used in topical, transdermal, and oral pharmaceutical preparations as an emulsifier and absorption enhancer. Recent studies in our laboratory have indicated that labrasol has a strong absorption enhancing effect on different types of drugs in vitro and in vivo. This study was performed to further elucidate the action mechanism of labrasol on the corneal penetration. In this research, the fluorescein sodium, a marker of passive paracellular transport of tight junction, was selected as the model drug to assess the effect of labrasol on in vitro corneal permeability. To investigate the continuous and real-time influence of labrasol on the membrane permeability and integrity, the Ussing chamber system was applied to monitor the electrophysiological parameters. And, furthermore, we elucidated the effect of labrasol on excised cornea at the molecular level by application of RT-PCR, Western blot, and immunohistochemical staining. The results indicated that labrasol obviously enhance the transcorneal permeability of fluorescein sodium, and the enhancement was realized by interacting with and down-regulating the associated proteins, such as Factin, claudin-1 and β-catenin, which were contributed to cell-cell connections, respectively.