title: Enantioselective skin permeation of ibuprofen enantiomers: mechanistic insights from ATR-FTIR and CLSM studies based on synthetic enantiomers as naphthalimide fluorescent probes.
abstract: OBJECTIVE
  The aim of this study was to investigate the mechanisms of different skin permeability of ibuprofen racemate and enantiomers.
  
  
  METHODS
  The percutaneous permeation of ibuprofen racemate and enantiomers through rabbit normal skin and damaged skin (without stratum corneum [SC]) was investigated in vitro 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.
  
  
  RESULTS
  The flux of (S)-ibuprofen through normal skin was significantly higher than that of (RS)-ibuprofen and (R)-ibuprofen (p < 0.05), whereas in damaged skin, there was no significant difference (p > 0.05). The predicted flux ratio of (S)-ibuprofen/(RS)-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Shenyang Pharmaceutical University, School of Pharmacy, Department of Pharmaceutical Science , 103 Wenhua Road, Shenyang 110016, Liaoning , China +86 24 23986330 ; fangliang2003@yahoo.com.
authors.forename: Qi-en
authors.initials: QE
authors.lastname: Che
authors.forename: Peng
authors.initials: P
authors.lastname: Quan
authors.forename: Mao
authors.initials: M
authors.lastname: Mu
authors.forename: Xinfu
authors.initials: X
authors.lastname: Zhang
authors.forename: Hanqing
authors.initials: H
authors.lastname: Zhao
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Song
authors.initials: S
authors.lastname: You
authors.forename: Yi
authors.initials: Y
authors.lastname: Xiao
authors.forename: Liang
authors.initials: L
authors.lastname: Fang
mesh_terms: D000818:Animals; D002152:Calorimetry, Differential Scanning; D004058:Diffusion; D004817:Epidermis / Q000378:metabolism; D005456:Fluorescent Dyes / Q000737:chemistry*; D007052:Ibuprofen / Q000493:pharmacokinetics*; D008297:Male; D018613:Microscopy, Confocal; D053644:Naphthalimides / Q000737:chemistry*; D010539:Permeability; D011817:Rabbits; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption / Q000187:drug effects*; D017550:Spectroscopy, Fourier Transform Infrared; D013237:Stereoisomerism; D013816:Thermodynamics
chemical_list: D005456:Fluorescent Dyes; D053644:Naphthalimides; D007052:Ibuprofen
keywords: (R)-(−)-ibuprofen; (S)-(+)-ibuprofen; enantiomers; enantioselective permeation; naphthalimide fluorescent probes