Mechanism of Ion-Pair Strategy in Modulating Skin Permeability of Zaltoprofen: Insight from Molecular-Level Resolution Based on Molecular Modeling and Confocal Laser Scanning Microscopy
Hongxia Cui
Department of Pharmaceutical Sciences, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016 China
Search for more papers by this authorPeng Quan
Department of Pharmaceutical Sciences, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016 China
Search for more papers by this authorHanqing Zhao
Department of Pharmaceutical Sciences, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016 China
Search for more papers by this authorXue Wen
School of Life Science and Bio-Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, 110016 China
Search for more papers by this authorWenting Song
Department of Pharmaceutical Sciences, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016 China
Search for more papers by this authorYi Xiao
State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, 116024 China
Search for more papers by this authorCorresponding Author
Yongshan Zhao
School of Life Science and Bio-Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, 110016 China
Telephone: +86-24-23986330; Fax: +86-24-23986330; E-mail: [email protected]; Telephone: +86-24-23986399; Fax: +86-24-23986431; E-mail: [email protected]Search for more papers by this authorCorresponding Author
Liang Fang
Department of Pharmaceutical Sciences, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016 China
Telephone: +86-24-23986330; Fax: +86-24-23986330; E-mail: [email protected]; Telephone: +86-24-23986399; Fax: +86-24-23986431; E-mail: [email protected]Search for more papers by this authorHongxia Cui
Department of Pharmaceutical Sciences, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016 China
Search for more papers by this authorPeng Quan
Department of Pharmaceutical Sciences, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016 China
Search for more papers by this authorHanqing Zhao
Department of Pharmaceutical Sciences, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016 China
Search for more papers by this authorXue Wen
School of Life Science and Bio-Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, 110016 China
Search for more papers by this authorWenting Song
Department of Pharmaceutical Sciences, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016 China
Search for more papers by this authorYi Xiao
State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, 116024 China
Search for more papers by this authorCorresponding Author
Yongshan Zhao
School of Life Science and Bio-Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, 110016 China
Telephone: +86-24-23986330; Fax: +86-24-23986330; E-mail: [email protected]; Telephone: +86-24-23986399; Fax: +86-24-23986431; E-mail: [email protected]Search for more papers by this authorCorresponding Author
Liang Fang
Department of Pharmaceutical Sciences, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016 China
Telephone: +86-24-23986330; Fax: +86-24-23986330; E-mail: [email protected]; Telephone: +86-24-23986399; Fax: +86-24-23986431; E-mail: [email protected]Search for more papers by this authorAbstract
The study was carried out to investigate the mechanism of the ion-pair strategy in modulating zaltoprofen (ZAL) skin permeability. Seven organic amines were chosen as counter ions and the formation of ion pairs was confirmed by Fourier transform infrared and proton nuclear magnetic resonance spectroscopy. In vitro permeation studies showed that the permeation of ZAL was significantly promoted with alkylamines and cycloalkanolamines, while significantly retarded with alkanolamines. The results were further visualized by confocal laser scanning microscopy studies. Investigations from the standpoint of solubility, partition, and diffusion indicated that the modulation mechanism of ion pairs was mainly attributed to an alteration of ZAL diffusion in the skin, which was accomplished by masking the carboxyl of ZAL and adding the hydrogen-bonding groups of counter ions. A negative correlation was observed between the enhancement ratio of ion pairs and the polar surface area of counter ions. Molecular modeling revealed that ion pairs acted with the nature of different affinity to ceramide, which would be responsible for the diffusion retardation. The study indicated that the maximum effect of ion pairs tended to be achieved with counter ions of lower hydrogen-bonding potential. Besides, ZAL–triethylamine ion pair might be a promising strategy for transdermal delivery of ZAL. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3395–3403, 2015
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