Ion-Pair Compounds of Strychnine for Enhancing Skin Permeability: Influencing the Transdermal Processes In Vitro Based on Molecular Simulation.

Lili He,Teng Zhang,Huaibo Tang,Di Xiong,Yan Liang,Xuewen Wu,Zhiming Wu,Lan Ma

doi:10.3390/ph15010034

Abstract

This research aimed to explore how Strychnine (Str) ion-pair compounds affect the in vitro transdermal process. In order to prevent the influence of different functional groups on skin permeation, seven homologous fatty acids were selected to form ion-pair compounds with Str. The in vitro permeation fluxes of the Str ion-pair compounds were 2.2 to 8.4 times that of Str, and Str-C10 had the highest permeation fluxes of 42.79 ± 19.86 µg/cm2/h. The hydrogen bond of the Str ion-pair compounds was also confirmed by Fourier Transform Infrared (FTIR) Spectroscopy, Nuclear Magnetic Resonance (NMR) Spectroscopy and molecular simulation. In the process of molecular simulation, the intercellular lipid and the viable skin were represented by ceramide, cholesterol and free fatty acid of equal molar ratios and water, respectively. It was found by the binding energy curve that the Str ion-pair compounds had better compatibility with the intercellular lipid and water than Str, which indicated that the affinity of Str ion-pair compounds and skin was better than that of Str and skin. Therefore, it was concluded that Str ion-pair compounds can be distributed from the vehicle to the intercellular lipid and viable skin more easily than Str. These findings broadened our knowledge about how Str ion-pair compounds affect the transdermal process.

Highlights

Strychnine (Str), as shown in Figure 1, is a traditional medicine comprised of spinal cord stimulant that is usually employed to treat hemiplegia and amblyopia by subcutaneous injection [1,2]
The zero-order absorption can be achieved by a transdermal drug delivery system (TDDS), which can be of significant therapeutic benefit for drugs having a narrow therapeutic index [5,6]
The Str-C10 had the most significant enhancing effect, with Q24 of 857.54 ± 157.84 μg/cm2. These results showed that the Str ion-pair compounds had obvious effects on permeation fluxes

Summary

Introduction

Strychnine (Str), as shown in Figure 1, is a traditional medicine comprised of spinal cord stimulant that is usually employed to treat hemiplegia and amblyopia by subcutaneous injection [1,2]. Strychnine (Str), as shown, is a traditional medicine comprised of spinal cord stimulant that is usually employed to treat hemiplegia and amblyopia by subcutaneous injection [1,2]. Str has a very narrow therapeutic index, it is known as a dangerous poison in spite of its therapeutic values. The zero-order absorption can be achieved by a transdermal drug delivery system (TDDS), which can be of significant therapeutic benefit for drugs having a narrow therapeutic index [5,6]. The skin comprising lipophilic stratum corneum (SC) and the aqueous living skin is a natural barrier that prevents drugs from entering the body. Appropriate solubility is helpful for the drug to be transported across the skin barrier

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