Skin Electrical Resistance Measurement of Oxygen-Containing Terpenes as Penetration Enhancers: Role of Stratum Corneum Lipids

Abstract

The measurement of skin electrical resistance (SER) has drawn a great deal of attention for the rapid screening of transdermal penetration enhancers (PEs). However, the mechanisms underlying the SER measurement are still unclear. This study was to investigate the effects and mechanisms of seven oxygen-containing terpenes on the SER kinetics. Stratum corneum (SC) lipids were proved to play a key role in SER measurement. Then, the factors affecting the SER measurement were optimized. By the determination of SER kinetics, cyclic terpenes (1,8-cineole, terpinen-4-ol, menthol and α-terpineol) were demonstrated to possess higher enhancement ratio (ER) values compared with linear terpenes (linalool, geraniol and citral). For the first time, the linear correlation was found between ER of terpenes and the interaction energy of terpene–ceramide complexes revealed by molecular simulation. The attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) analysis revealed that the effect of cyclic terpenes on SC lipid arrangement was obviously stronger than that of linear terpenes. In addition, by evaluating HaCaT skin cell viability, little difference was found between the toxicities of cyclic and linear terpenes. In conclusion, measurement of SER could be a feasible approach for the efficient evaluation of the PEs that mainly act on SC lipids.

Natural Ingredients of Transdermal Drug Delivery Systems as Permeation Enhancers of Active Substances through the Stratum Corneum

“…Zhu et al evaluated seven oxygen-containing terpenes (1,8-cineole, citral, geraniol, linalool, menthol, terpinen-4-ol, and α-terpineol) at a concentration of 5%; both cyclic and linear forms were evaluated using the method of measuring skin electrical resistance (SER), the changes of which reflect the degree of skin integrity after application of compounds considered to be API permeation enhancers. , Cyclic terpenes (1,8-cineole, terpinen-4-ol, menthol, and α-terpineol) were shown to reduce SER values and impair the skin’s barrier function to a greater extent than linear terpenes (linalool, geraniol, and citral). Molecular computer simulations indicated that the SER values for cyclic terpenes were associated with the formation of stronger hydrogen bonds with the polar head of SC ceramides creating a pathway for hydrophilic API penetration (LogP > 3), as well as a pathway for water to escape through the epidermis. , …”

“…62 FTIR (Fourier-transform infrared spectroscopy) results confirmed that limonene interacts with the alkyl chain region of SC lipids causing an increase in fluidization, as it relaxes the lamellar organization of the lipids. 170 Zhu et al 171 evaluated seven oxygen-containing terpenes (1,8cineole, citral, geraniol, linalool, menthol, terpinen-4-ol, and αterpineol) at a concentration of 5%; both cyclic and linear forms were evaluated using the method of measuring skin electrical resistance (SER), the changes of which reflect the degree of skin integrity after application of compounds considered to be API permeation enhancers. 172,173 Cyclic terpenes (1,8-cineole, terpinen-4-ol, menthol, and α-terpineol) were shown to reduce SER values and impair the skin's barrier function to a greater extent than linear terpenes (linalool, geraniol, and citral).…”

“…Molecular computer simulations indicated that the SER values for cyclic terpenes were associated with the formation of stronger hydrogen bonds with the polar head of SC ceramides 171 creating a pathway for hydrophilic API penetration (LogP > 3), as well as a pathway for water to escape through the epidermis. 171,174 In an in vitro study conducted in Franz diffusion cells, differences in the enhancement of ligustrazine hydrochloride permeation using the monocyclic monoterpenes menthol (Table 2, item 10) and menthone (Table 2, item 11) were assessed. Menthol contains a hydroxyl group attached to its ring and was found to be more effective than menthone with a carbonyl group.…”

In Vitro Activity of Essential Oils Distilled from Colombian Plants against Candidaauris and Other Candida Species with Different Antifungal Susceptibility Profiles

“…Other studies have also evaluated the cytotoxicity of the EOs distilled from plants not belonging to the genus Lippia and from the terpenes studied here on the HaCaT cell line, with CC 50 values ranging between 33.93 and 1701.97 μg/mL [ 42 , 43 , 44 ]. The CC 50 values obtained in our study with the Lippia spp.…”

Effect of Penetration Enhancer on the Structure of Stratum Corneum: On-Site Study by Confocal Polarized Raman Imaging

“…Histology, 6 small-angle X-ray scattering (SAXS), 7,8 and fluorescence spectroscopy 9 are often destructive or are performed under nonphysiological conditions. To overcome these drawbacks, a variety of label-free optical techniques have been used to measure the components and structure of SC, including multiphoton imaging, 10,11 Fourier transform infrared (FT-IR) spectroscopy, 12,13 and Raman spectroscopy (RS). 7,14−20 Confocal Raman spectroscopy (CRS) is widely accepted as a non-invasive, label-free, accurate, and fast technique for chemical composition determination, 14,15 biological imaging, 18,19 and SC studies.…”