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. 2017:2017:7409420.
doi: 10.1155/2017/7409420. Epub 2017 Feb 21.

High-Throughput Screening of Potential Skin Penetration-Enhancers Using Stratum Corneum Lipid Liposomes: Preliminary Evaluation for Different Concentrations of Ethanol

Pajaree Sakdiset  1 , Yuki Kitao  2 , Hiroaki Todo  2 , Kenji Sugibayashi  2
Affiliations

High-Throughput Screening of Potential Skin Penetration-Enhancers Using Stratum Corneum Lipid Liposomes: Preliminary Evaluation for Different Concentrations of Ethanol

Pajaree Sakdiset et al. J Pharm (Cairo). 2017.

Abstract

In this study, we developed a technique for high-throughput screening (HTS) of skin penetration-enhancers using stratum corneum lipid liposomes (SCLLs). A fluorescent marker, sodium fluorescein (FL), entrapped in SCLLs was prepared to provide a preliminary evaluation of the effect of different concentrations of ethanol on the disruption effect of SCLLs, which is an alternative for skin penetration-enhancing effects. In addition, SCLLs containing a fluorescent probe (DPH, TMA-DPH, or ANS) were also prepared and utilized to investigate SCLL fluidity. The results using SCLL-based techniques were compared with conventional skin permeation and skin impedance test using hairless rat skin. The obtained correlations were validated between FL leakage, SCLL fluidity with various probes, or skin impedance and increases in the skin permeation enhancement ratio (ER) of caffeine as a model penetrant. As a result, FL leakage and SCLL fluidity using ANS were considered to be good indices for the skin penetration-enhancing effect, suggesting that the action of ethanol on the SC lipid and penetration-enhancing is mainly on the polar head group of intercellular lipids. In addition, this screening method using SCLL could be utilized as an alternative HTS technique for conventional animal tests. Simultaneously, the method was found to be time-saving and sensitive compared with a direct assay using human and animal skins.

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Conflict of interest statement

The authors declare that there is no conflict of interests.

Figures

Figure 1
Figure 1
Time course of cumulative amount of caffeine permeated through full-thickness hairless rat skin after application with different concentrations of ethanol. Each value represents the mean ± SE (n = 3–5).
Figure 2
Figure 2
Effect of ethanol concentration on the increase in the skin-penetration-enhancement ratio (ER) of caffeine permeated over 8 h. Each value represents the mean ± SE (n = 3–5).
Figure 3
Figure 3
Effect of different concentrations of ethanol on the percentage of skin impedance reduction. Each value represents the mean ± SE (n = 3–5).
Figure 4
Figure 4
Effect of different concentrations of ethanol on the sodium fluorescein (FL) leakage from stratum corneum lipid liposomes (SCLLs). Each value represents the mean ± SE (n = 3).
Figure 5
Figure 5
Effect of different concentrations of ethanol on the percentage decrease in fluorescence polarization (Pf) using three fluorescent probes: 1,6-diphenyl-1,3,5-hexatriene (DPH), N,N,N-trimethyl-4-(6-phenyl-1,3,5-hexatrien-1-yl)phenyl-ammonium p-toluenesulfonate (TMA-DPH), and 8-anilino-1-naphthalenesulfonic acid ammonium salt (ANS). Each value represents the mean ± SE (n = 3).
Figure 6
Figure 6
The relationship between sodium fluorescein (FL) leakage and increase in the skin penetration-enhancement ratio (ER) (a); log⁡ER of caffeine permeated over 8 h from each concentration of ethanol solution (b). Each value represents the mean ± SE (n = 3–5).
Figure 7
Figure 7
The relationship between percentage of decrease in fluorescence polarization (Pf) using various fluorescent probes and increase in the skin penetration-enhancement ratio (ER) (a); log⁡ER of caffeine permeated over 8 h from each concentration of ethanol solution (b). Each value represents the mean ± SE (n = 3–5). The data from 100% ethanol was excluded in this figure.
Figure 8
Figure 8
The relationship between skin impedance reduction and increase in the skin penetration-enhancement ratio (ER) (a); log⁡ER of caffeine permeated over 8 h from each concentration of ethanol solution (b). Each value represents the mean ± SE (n = 3–5).
Figure 9
Figure 9
Location of fluorescent probes in stratum corneum lipid liposomes (SCLLs).
See this image and copyright information in PMC

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