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Topical skin formulations often include penetration enhancers that interact with the outer stratum corneum (SC) layer to chemically enhance diffusion. Alternatively, penetration can be mechanically enhanced with simple rubbing in the presence of solid particles sometimes included to exfoliate the top layers of the SC. Our goal was to evaluate micron-sized carbon dioxide bubbles included in a foamed moisturizing formulation as a mechanical penetration enhancement strategy. We show that moisturizing foam bubbles cause an increase in SC formulation penetration using both mechanical and spectroscopic characterization. Our results suggest viscous liquid film drainage between coalescing gaseous bubbles creates local regions of increased hydrodynamic pressure in the foam liquid layer adjacent to the SC surface that enhances treatment penetration. An SC molecular diffusion model is used to rationalize the observed behavior. The findings indicate marked increased levels of treatment concentration in the SC at 2 h and that persists to 18 h after exposure, far exceeding non-foamed treatments. The study suggests an alternate strategy for increasing formulation penetration with a non-chemical mechanism., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The barrier function of the skin mainly relies on its outermost layer, the stratum corneum (SC), which is a lipid-protein composite biomaterial. In addition, SC contains a mixture of small polar compounds, the natural moisturizing factor (NMF). Most of the NMF components are solid at ambient relative humidities (RHs). We herein raise the question of what the effects of adding a mixture of chemicals to the SC are as compared to adding the single components. We use mixtures of glucose and NaCl, both present in NMF and in skin formulations, and the effects on SC were studied using solid-state NMR, wide angle X-ray diffraction, and sorption microbalance. The deliquescence RHs of the glucose-NaCl mixtures are lower than the individual chemicals. The same trend is also seen when these chemicals are added to SC, as the dissolution occurs at lower RH for the mixture than for the single chemicals. Notably, the mixtures can also increase the mobility of SC lipids and proteins more than the individual compounds. These data illustrate a synergistic effect by adding a mixture rather than a single polar compound to the SC, which may also have implications for the complex mixture NMF inside SC in dry conditions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Moisturizing compounds are commonly applied topically to human stratum corneum (SC). Many types of molecular species are employed, most commonly including humectants and occlusives. We find new evidence of keratin dispersion caused by the moisturizing compound ectoine (1,4,5,6-tetrahydro-2-methyl-4-pyrimidinecarboxylic acid), and provide the first characterization of its impacts on the hydration kinetics and biomechanics of SC. A second compound, 2-(2-hydroxyethoxy)ethylguanidine succinate (HEG) was investigated for comparison. A suite of biomechanical and biochemical assays including FTIR, drying stress, and cellular cohesion were used. Studies were conducted on normal, lipid-extracted, and lipid plus natural moisturizing factor extracted SC. Ectoine was found to improve the dispersity and hydration of keratin bundles in corneocytes. It also decreased rates of stress development in lipid extracted SC when exposed to a dry environment by ∼30% while improving stress reduction during rehydration by ∼20%. Peak stresses were increased in harsh drying environments of <5% RH, but SC swelling measurements suggest that water retention was improved in ambient conditions. Further, changes up to ∼4 J/m 2 were seen in cohesion after ectoine treatments, suggesting corneodesmosome interactions. HEG was tested and found to disperse keratin without impacting corneodesmosomes. These results indicate that keratin dispersants produce beneficial effects on SC hydration kinetics, ultimately resulting in higher SC hydration under ambient conditions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Published by Elsevier B.V.)

Background: The lipid components and natural moisturizing factors (NMFs) of the stratum corneum (SC) are integral pieces of the self-regulating barrier strategy which comprises one of the most important functions of human skin and seems to be related to biomechanical responses of the SC., Objectives: This work presents the contributions of the lipid bilayers and NMFs to the barrier properties and mechanical responses of human SC., Methods: We performed 2 biomechanical experiments, substrate curvature testing and double cantilever beam cohesion measurements, on isolated human SC exposed to either water, a 1:1 mixture of acetone/ether, or a 1:1 mixture of chloroform/methanol for various durations., Results: We show that treating ex vivo SC with organic solvents results in lipid extraction which increases with duration of exposure. This extraction is tied to a remarkably linear increase in the levels and rates of biaxial stress development during drying/hydration cycles. This effect appears to be tied to the total amounts of lipids extracted. Furthermore, striking changes are seen in the intercellular cohesion properties of the tissue after solvent exposure. Interestingly, changes in drying stress profiles are not observed after treatment with water, which has been previously shown to remove NMFs from the tissue, and which therefore might be expected to induce changes in the drying behavior of the skin. However, changes in intercellular cohesion and the SC cohesion gradient are seen, suggesting impacts on the corneodesmosome protein binding junctions within the tissue., Conclusions: These results suggest that lipid loss causes marked increases in SC drying stresses, which may in turn contribute to changes in skin perception. NMF extraction may be important in vivo, but has remarkably little impact in isolated SC., (© 2020 S. Karger AG, Basel.)

A new approach towards the synthesis of indole derivatives via triflic acid-promoted cycloisomerization with rearrangement of 2-(alkyn-1-yl)phenyl isothiocyanates and 2-(alkyn-1-yl)phenyl isocyanates has been achieved. By this methodology, structurally diverse types of indole derivatives such as thieno- and furo-indoles, spiro-indolethiones, spiro-oxindoles, and 3-alkylidene-oxindoles were synthesized.