title: [Effects of D-limonene and L-limonene on transdermal absorption of ligustrazine hydrochloride].
abstract: OBJECTIVE
  To investigate the effects and permeation mechanism of D-limonene and L-limonene on transdermal delivery of ligustrazine hydrochloride (LH).
  
  
  METHODS
  Transdermal flux of LH through porcine skin was determined in vitro by Franz-type diffusion cells. The peak shift and peak areas of C-H stretching vibration absorption were estimated by Fourier transform-infrared (FTIR). Morphological changes in the stratum corneum (SC) treated with enhancers were observed by a scanning electron microscope (SEM) and apparent density, a new concept, was proposed to estimate the desquamated extent of SC for the first time.
  
  
  RESULTS
  There were no statistic difference (P > 0.05) between the transdermal fluxs of the enantiomer enhancers which were higher than those of control and azone. But the lag time of L-limonene was 2.55 times than that of D-limonene. The FTIR results revealed that the shift and decreased peak area of C-H stretching vibrations in the SC lipids were dependent on the enhancers. The enantiomers permeation enhancers, D-limonene and L-limonene, were able to perturb and extract the SC lipids to different extent. The disordering and extracting lipids activity of L-limonene was stronger than that of D-limonene. SEM studies demonstrated that the extraction of lipids was depended on the selected penetration promoters.
  
  
  CONCLUSIONS
  D-limonene was the most effective enhancer which had the greater transdermal flux of LH and the least lag time. The results showed that the permeation enhancement mechanism of the enantiomer enhancers to LH was multiple ones including disordering and extracting the SC lipids and probably including stereoselective mechanism.
authors.affiliation: School of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing 210009, China. zhangchunfeng67@163.com
authors.forename: Chun-feng
authors.initials: CF
authors.lastname: Zhang
authors.forename: Zhong-lin
authors.initials: ZL
authors.lastname: Yang
authors.forename: Jia-bo
authors.initials: JB
authors.lastname: Luo
mesh_terms: D000818:Animals; D053138:Cyclohexenes / Q000494:pharmacology*; D030004:Ligusticum / Q000737:chemistry; D000077222:Limonene; D008855:Microscopy, Electron, Scanning; D010946:Plants, Medicinal / Q000737:chemistry; D011719:Pyrazines / Q000302:isolation & purification / Q000493:pharmacokinetics*; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D012869:Skin Absorption / Q000187:drug effects*; D013237:Stereoisomerism; D013552:Swine; D013556:Swine, Miniature; D013729:Terpenes / Q000494:pharmacology*
chemical_list: D053138:Cyclohexenes; D011719:Pyrazines; D013729:Terpenes; D000077222:Limonene; C017953:tetramethylpyrazine