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

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.

Characterization of Classical Flexural and Nummular Forms of Atopic Dermatitis in Childhood with Regard to Anamnestic, Clinical and Epidermal Barrier Aspects

Nummular (coin-shaped) and classical (flexural) atopic dermatitis differ morphologically, but no other distinguishing features are known. The aim of this study was to determine differences and similarities of both variants in children. Detailed interviews, clinical examinations, biophysical measurements and electron microscopic analyses were performed on 10 children with nummular atopic dermatitis, 14 with classical atopic dermatitis and 10 healthy controls. Nummular atopic dermatitis affected more boys than girls and manifested less frequently within the first year of life than classical atopic dermatitis. Localization, distribution and morphology of the eczema varied more over time, and expression of keratosis pilaris was more severe in children with nummular atopic dermatitis. Both disease groups showed reduced hydration, increased transepidermal water loss and reduced intercellular lipid lamellae in lesional skin areas compared with non-lesional areas. These findings underline the separate classification of both variants. Further research is necessary to investigate the potential of diverging therapeutic approaches.

Effect of Lactic Fermentation Products on Human Epidermal Cell Differentiation, Ceramide Content, and Amino Acid Production

<b><i>Introduction:</i></b> Lactic fermentation products (LFPs) are thought to affect “good” bacteria in the gut. We previously reported that oral administration of LFPs has beneficial therapeutic effects in a mouse model of atopic dermatitis. However, it is unclear how LFPs affect human epidermal cell differentiation, ceramide (Cer), and amino acid production. <b><i>Objective:</i></b> The aim of this study was to determine the effects of LFPs on epidermal cell differentiation, by assessing amino acid and Cer production. <b><i>Methods:</i></b> A 3-dimensional cultured human epidermis model and normal human epidermal keratinocytes were used. Cytotoxicity tests were performed using alamar Blue. Transepidermal water loss (TEWL) was used as an index to assess barrier function. Keratin 1 (K1), keratin 5 (K5), keratin 10 (K10), involucrin (INV), calpain 1, and transglutaminase (TGase) (markers of differentiation) and profilaggrin (proFLG) and bleomycin hydrolase (amino acid synthesis-related genes) expression levels were quantified by RT-PCR. In addition, TGase protein levels were measured by Western blotting. The intercellular lipid content of the stratum corneum was measured by high-performance thin-layer chromatography. Amino acids were quantified using an amino acid analyzer. Finally, bound water content in the stratum corneum was measured by differential scanning calorimetry. <b><i>Results:</i></b> Cell viability did not change, but TEWL was significantly decreased in the cells treated with LFPs compared with the control cells. Treatment with LFPs significantly increased expression of the late-differentiation markers INV and TGase at the RNA level. Furthermore, TGase protein expression was significantly increased by treatment with LFPs. Treating a 3-dimensional cultured epidermis model with LFPs significantly increased the intercellular lipid content of the stratum corneum and production of the amino acid arginine (Arg). The amount of bound water in the stratum corneum was increased significantly in the LFP application group. <b><i>Conclusion:</i></b> Treatment with LFPs promotes human epidermal cell differentiation and increases the intercellular content of the free fatty acid, Chol, Cer [NS], Cer [AS], and Cer [AP]. This may result in improved skin barrier function. The increased amount of Arg observed in keratinocytes may help improve water retention.