Enantioselective skin permeation of ibuprofen enantiomers: mechanistic insights from ATR-FTIR and CLSM studies based on synthetic enantiomers as naphthalimide fluorescent probes. (October 2014)

• Record Type: Journal Article
• Authors: Che, Qi-en; Quan, Peng; Mu, Mao; Zhang, Xinfu; Zhao, Hanqing; Zhang, Yu; You, Song; Xiao, Yi; Fang, Liang
• Is Part Of: Expert opinion on drug delivery. Volume 11:Number 10(2014:Oct.)
• Page Start: 1513
• Page End: 1523
• Publication Date: 2014-10
• Subjects: Drug delivery devices -- Periodicals; Drug delivery systems -- Periodicals; 615.605
• DOI: 10.1517/17425247.2014.929661
• Languages: English
• ISSNs: 1742-5247

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p> <bold> <italic>Objective: </italic> </bold>The aim of this study was to investigate the mechanisms of different skin permeability of ibuprofen racemate and enantiomers.</p> <p> <bold> <italic>Methods:</italic> </bold> The percutaneous permeation of ibuprofen racemate and enantiomers through rabbit normal skin and damaged skin (without stratum corneum [SC]) was investigated <italic>in vitro</italic> using side-by-side diffusion cells. With the melting temperature-membrane transport model, the flux ratio of enantiomer/racemate was calculated from their thermodynamic properties obtained by differential scanning calorimetry. Attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) study was performed to evaluate the interaction between the enantiomers and the SC. New fluorescent probes were designed and utilized in confocal laser scanning microscopy (CLSM) study for visualization of the enantioselective permeation of the enantiomers through the intact rabbit skin.</p> <p> <bold> <italic>Result:</italic> </bold> The flux of <italic>(S)</italic>-ibuprofen through normal skin was significantly higher than that of <italic>(RS)</italic>-ibuprofen and <italic>(R)</italic>-ibuprofen (p < 0.05), whereas in damaged skin, there was no significant difference (p > 0.05). The predicted flux ratio of <italic>(S)</italic>-ibuprofen/<italic>(RS)</italic>-ibuprofen (2.50) was in close agreement with the experimentally determined ratio (2.48). These results were supported by ATR-FTIR and CLSM studies that indicated that a chiral environment of the skin led to the enantioselective permeation of enantiomers.</p> <p> <bold> <italic>Conclusions:</italic> </bold> The chiral nature of the SC and the different physicochemical properties of the enantiomers should be taken into account in the assessment of different skin permeability of the racemate and enantiomers. The synthetic fluorescent probes used in this study could visualize the enantioselective permeation of the chiral compounds across the skin.</p> </abstract>