Effects of cinnamene enhancers on transdermal delivery of ligustrazine hydrochloride.
Cinnamene compounds, cinnamic acid, cinnamaldehyde and cinnamic alcohol, were employed as enhancers. The effects and mechanisms of penetration promoters on the in vitro percutaneous absorption of ligustrazine hydrochloride across hairless porcine dorsal skin were investigated. Transdermal fluxes of ligustrazine hydrochloride through porcine skin were determined in vitro by Franz-type diffusion cells. The results indicated that the penetration flux of ligustrazine hydrochloride by cinnamic acid was the greatest. Significant statistical differences (P<0.05) were found between cinnamic acid and other promoters. Fourier transform-infrared (FT-IR) were carried out to analyze the effects of enhancers on the biophysical properties of the stratum corneum and the permeation enhancement mechanisms. FT-IR results revealed that the changes of peak shift and peak area due to C-H stretching vibrations in the stratum corneum lipids were associated with the selected enhancers. All of them could perturb and extract the stratum corneum lipids to different extent. Morphological changes of the skin treated with enhancers were monitored by a scanning electron microscope. It was demonstrated that the extraction of the stratum corneum lipids by the enhancers led to the disruption of stratum corneum and the desquamation of stratum corneum flake. Apparent density was newly proposed to estimate the desquamated extent of stratum corneum flake. Correlation analysis revealed that there was a linear relationship between apparent density and decrease in peak area. The results showed that the permeation enhancement mechanisms of cinnamene were pleiotropic ones, including disordering the lipids, extracting the lipids and competitive hydrogen bonding between cinnamene enhancers and amides of ceramide head groups in stratum corneum.
Zhang
Chun-feng
CF
School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China. zhangchungfeng67@163.com
Yang
Zhong-lin
ZL
Luo
Jia-bo
JB
Zhu
Quan-hong
QH
Zhao
Hui-nan
HN
D000279:Administration, Cutaneous; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002934:Cinnamates / Q000737:chemistry*; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D008055:Lipids / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D008956:Models, Chemical; D011719:Pyrazines / Q000008:administration & dosage* / Q000737:chemistry; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012869:Skin Absorption; D013055:Spectrophotometry, Infrared; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D013552:Swine
D002934:Cinnamates; D005343:Fibrinolytic Agents; D008055:Lipids; D011719:Pyrazines; C029010:cinnamic acid; C017953:tetramethylpyrazine