Stratum corneum molecular mobility in the presence of natural moisturizers (original) (raw)
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Characterization of Stratum Corneum Molecular Dynamics by Natural-Abundance 13C Solid-State NMR
PLoS ONE, 2013
Despite the enormous potential for pharmaceutical applications, there is still a lack of understanding of the molecular details that can contribute to increased permeability of the stratum corneum (SC). To investigate the influence of hydration and heating on the SC, we record the natural-abundance 13 C signal of SC using polarization transfer solid-state NMR methods. Resonance lines from all major SC components are assigned. Comparison of the signal intensities obtained with the INEPT and CP pulse sequences gives information on the molecular dynamics of SC components. The majority of the lipids are rigid at 32uC, and those lipids co-exist with a small pool of mobile lipids. The ratio between mobile and rigid lipids increases with hydration. An abrupt change of keratin filament dynamics occurs at RH = 80-85%, from completely rigid to a structure with rigid backbone and mobile protruding terminals. Heating has a strong effect on the lipid mobility, but only a weak influence on the keratin filaments. The results provide novel molecular insight into how the SC constituents are affected by hydration and heating, and improve the understanding of enhanced SC permeability, which is associated with elevated temperatures and SC hydration.
Proceedings of the National Academy of Sciences of the United States of America, 2017
Solvents are commonly used in pharmaceutical and cosmetic formulations and sanitary products and cleansers. The uptake of solvent into the skin may change the molecular organization of skin lipids and proteins, which may in turn alter the protective skin barrier function. We herein examine the molecular effects of 10 different solvents on the outermost layer of skin, the stratum corneum (SC), using polarization transfer solid-state NMR on natural abundance (13)C in intact SC. With this approach it is possible to characterize the molecular dynamics of solvent molecules when present inside intact SC and to simultaneously monitor the effects caused by the added solvent on SC lipids and protein components. All solvents investigated cause an increased fluidity of SC lipids, with the most prominent effects shown for the apolar hydrocarbon solvents and 2-propanol. However, no solvent other than water shows the ability to fluidize amino acids in the keratin filaments. The solvent molecules ...
Physical Chemistry Chemical Physics, 2020
The outermost layer of the skin is the stratum corneum (SC), which is mainly comprised of solid proteins and lipids. Minor amounts of mobile proteins and lipids are crucial for the macroscopic properties of the SC, including softness, elasticity and barrier function. Still this minor number of mobile components are not well characterized in terms of structure or amount. Conventional quantitative direct polarization (Q-DP) 13 C solid-state NMR gives signal amplitudes proportional to concentrations, but fails to quantify the SC mobile components because of spectral overlap with the overwhelming signals from the solids. Spectral editing with the INEPT scheme suppresses the signals from solids, but also modulates the amplitudes of the mobile components depending on their values of the transverse relaxation times T 2 , scalar couplings J CH , and number of covalently bound hydrogens n H. This study describes a quantitative INEPT (Q-INEPT) method relying on systematic variation of the INEPT timing variables to estimate T 2 , J CH , n H , and amplitude for each of the resolved resonances from the mobile components. Q-INEPT is validated with a series of model systems containing molecules with different hydrophobicity and dynamics. For selected systems where Q-DP is applicable, the results of Q-INEPT and Q-DP are similar with respect to the linearity and uncertainty of the obtained molar ratios. Utilizing a reference compound with known concentration, we quantify the concentrations of mobile lipids and proteins within the mainly solid SC. By melting all lipids at high temperature, we obtain the total lipid concentration. These Q-INEPT results are the first steps towards a quantitative understanding of the relations between mobile component concentrations and SC macroscopic properties.
Biochimica et Biophysica Acta (BBA) - Biomembranes, 2007
The outermost layer of skin, stratum corneum (SC), functions as the major barrier to diffusion. SC has the architecture of dead keratin filled cells embedded in a lipid matrix. This work presents a detailed study of the hydration process in extracted SC lipids, isolated corneocytes and intact SC. Using isothermal sorption microcalorimetry and relaxation and wideline 1 H NMR, we study these systems at varying degrees of hydration/relative humidities (RH) at 25°C. The basic findings are (i) there is a substantial swelling both of SC lipids, the corneocytes and the intact SC at high RH. At low RHs corneocytes take up more water than SC lipids do, while at high RHs swelling of SC lipids is more pronounced than that of corneocytes. (ii) Lipids in a fluid state are present in both extracted SC lipids and in the intact SC. (iii) The fraction of fluid lipids is lower at 1.4% water content than at 15% but remains virtually constant as the water content is further increased. (iv) Three exothermic phase transitions are detected in the SC lipids at RH = 91-94%, and we speculate that the lipid re-organization is responsible for the hydration-induced variations in SC permeability. (v) The hydration causes swelling in the corneocytes, while it does not affect the mobility of solid components (keratin filaments).
Glycerol and urea can be used to increase skin permeability in reduced hydration conditions
European Journal of Pharmaceutical Sciences, 2013
The natural moisturizing factor (NMF) is a group of hygroscopic molecules that is naturally present in skin and protects from severe drying. Glycerol and urea are two examples of NMF components that are also used in skin care applications. In the present study, we investigate the influence of glycerol and urea on the permeability of a model drug (metronidazole, Mz) across excised pig skin membranes at different hydrating conditions. The degree of skin hydration is regulated by the gradient in water activity across the membrane, which in turn depends on the water activity of the formulation in contact with the skin membrane. Here, we determine the water activity of all formulations employed using an isothermal calorimetric method. Thus, the gradient in water activity is controlled by a novel experimental set-up with well-defined boundary conditions on both sides of the skin membrane. The results demonstrate that glycerol and urea can retain high steady state flux of Mz across skin membranes at dehydrating conditions, which otherwise would decrease the permeability due to dehydration. X-ray diffraction measurements are performed to give insight into the effects of glycerol and urea on SC molecular organization. The novel steady state flux results can be related to the observation that water, glycerol, and urea all affect the structural features of the SC molecular components in a similar manner.
Chain Length of Free Fatty Acids Influences the Phase Behavior of Stratum Corneum Model Membranes
Langmuir : the ACS journal of surfaces and colloids, 2015
The skin, the largest organ of the human body, forms a flexible interface between our internal and external environment that protects our organism from exogenous compounds as well as excessive water loss. The stratum corneum (SC), the outermost layer of mammal epidermis, is mainly responsible for the skin impermeability. The SC is formed by corneocytes embedded in a lipid matrix, which is mostly constituted of ceramides (Cer), free fatty acids (FFA), and cholesterol (Chol), organized in two coexisting crystalline lamellar phases. This arrangement of lipids is crucial to skin barrier function. The aim of this paper is to determine the impact of FFA chain length on the phase behavior of SC model lipid membranes using solid-state deuterium NMR and IR spectroscopy. We studied ternary mixtures of N-lignoceroyl-d-erythro-sphingosine (Cer24), cholesterol, and palmitic (FFA16) or lignoceric (FFA24) acid in an equimolar ratio. This proportion replicates the lipid composition found in the SC ...
Scientific reports, 2017
Hydration is a key aspect of the skin that influences its physical and mechanical properties. Here, we investigate the interplay between molecular and macroscopic properties of the outer skin layer - the stratum corneum (SC) and how this varies with hydration. It is shown that hydration leads to changes in the molecular arrangement of the peptides in the keratin filaments as well as dynamics of C-H bond reorientation of amino acids in the protruding terminals of keratin protein within the SC. The changes in molecular structure and dynamics occur at a threshold hydration corresponding to ca. 85% relative humidity (RH). The abrupt changes in SC molecular properties coincide with changes in SC macroscopic swelling properties as well as mechanical properties in the SC. The flexible terminals at the solid keratin filaments can be compared to flexible polymer brushes in colloidal systems, creating long-range repulsion and extensive swelling in water. We further show that the addition of u...
Biochimica et Biophysica Acta (BBA) - Biomembranes, 2012
Ethanol is used in a variety of topical products. It is known to enhance the permeability of the skin by altering the ability of the stratum corneum (SC) intercellular membranes to form an effective barrier. In addition, ethanol and other alcohols are key components of antiseptic gels currently used for hand wash. Using infrared and deuterium NMR spectroscopy as well as calorimetry, we have investigated the effect of ethanol on a model membrane composed of lipids representing the three classes of SC lipids, an equimolar mixture of N-palmitoylsphingosine (ceramide), palmitic acid and cholesterol. Ethanol is found to influence the membrane in a dose dependent manner, disrupting packing and increasing lipid motion at low concentrations and selectively extracting lipids at moderate concentrations.
Molecules, 2018
The skin permeability (Kp) defines the rate of a chemical penetrating across the stratum corneum. This value is widely used to quantitatively describe the transport of molecules in the outermost layer of epidermal skin and indicate the significance of skin absorption. This study defined a Kp quantitative structure-activity relationship (QSAR) based on 106 chemical substances of Kp measured using human skin and interpreted the molecular interactions underlying transport behavior of small molecules in the stratum corneum. The Kp QSAR developed in this study identified four molecular descriptors that described the molecular cyclicity in the molecule reflecting local geometrical environments, topological distances between pairs of oxygen and chlorine atoms, lipophilicity, and similarity to antineoplastics in molecular properties. This Kp QSAR considered the octanol-water partition coefficient to be a direct influence on transdermal movement of molecules. Moreover, the Kp QSAR identified a sub-domain of molecular properties initially defined to describe the antineoplastic resemblance of a compound as a significant factor in affecting transdermal permeation of solutes. This finding suggests that the influence of molecular size on the chemical's skin-permeating capability should be interpreted with other relevant physicochemical properties rather than being represented by molecular weight alone.