Effect of (E)-2-isopropyl-5-methylcyclohexyl octadec-9-enoate on transdermal delivery of Aconitum alkaloids

Abstract

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. Conclusion: The results showed that M-OA was worthy of further investigation as a potential candidate for inclusion in transdermal formulations as a penetration enhancer.

• Aconitum alkaloids
• ATR-FTIR
• l-menthol
• oleic acid
• SEM

Acknowledgment

The authors thank Professor Yasunori Morimoto, Faculty of Pharmaceutical Sciences, Josai University, Japan, for providing the two-chamber diffusion cells.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.