Effect of (E)-2-isopropyl-5-methylcyclohexyl octadec-9-enoate on transdermal delivery of Aconitum alkaloids.
OBJECTIVE
The aim of this work was to evaluate the percutaneous absorption of Aconitum alkaloids using (E)-2-isopropyl-5-methylcyclohexyl octadec-9-enoate (M-OA) as an enhancer as well as to investigate the effect of M-OA in isopropyl palmitate (IPP) solution (5% ethanol in IPP, w/v), with or without an enhancer, on the stratum corneum (SC) barrier properties in vitro.


METHODS
The in vitro permeation studies of Aconitum alkaloids were conducted in isopropyl myristate (IPM) solution in side-by-side diffusion cells. In addition, scanning electron microscopy (SEM) and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy were used to evaluate the M-OA biophysical changes in SC barrier function in vitro.


RESULTS
The in vitro permeation studies indicated that M-OA had significant enhancing effect on the permeation of mesaconitine (MA) and hypaconitine (HA); however, aconitine (AC) was too low to be detected on the receiver side, and L-menthol had no effect on the penetration of all the Aconitum alkaloids. Morphological changes in the skin after enhancer treatment demonstrated that the extraction of the SC lipids by the enhancers led to disruption of the SC and the desquamation of SC flake. ATR-FTIR spectra of C-H asymmetric/symmetric stretching peak shifts and amide II stretching vibrations were indicative of SC lipid fluidization and changes in protein conformation, respectively.


CONCLUSIONS
The results showed that M-OA was worthy of further investigation as a potential candidate for inclusion in transdermal formulations as a penetration enhancer.
Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, Liaoning, China.
Ligang
L
Zhao
Liang
L
Fang
Yan
Y
Li
Ni
N
Zheng
Yongnan
Y
Xu
Jinghua
J
Wang
Zhonggui
Z
He
D000157:Aconitine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D031841:Aconitum / Q000737:chemistry; D000279:Administration, Cutaneous; D000818:Animals; D005079:Excipients / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry; D008297:Male; D009829:Oleic Acids / Q000737:chemistry*; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000187:drug effects; D012869:Skin Absorption; D012995:Solubility
C559968:(E)-2-isopropyl-5-methylcyclohexyl octadec-9-enoate; D005079:Excipients; D008055:Lipids; D009829:Oleic Acids; C058309:hypaconitine; C019470:mesaconitine; D000157:Aconitine