Tracking solvents in the skin through atomically resolved measurements of molecular mobility in intact stratum corneum

Abstract

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 13C 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 themselves show reduced molecular mobility when incorporated in the SC matrix. Changes in the molecular properties of the SC, and in particular alternation in the balance between solid and fluid SC components, may have significant influences on the macroscopic SC barrier properties as well as mechanical properties of the skin. Deepened understanding of molecular effects of foreign compounds in SC fluidity can therefore have strong impact on the development of skin products in pharmaceutical, cosmetic, and sanitary applications.

Specific barrier response profiles after experimentally induced skin irritation in vivo

“…Also, n‐propanol is known to induce changes in the SC; for example, it has pronounced denaturing effects on the SC proteins, profilaggrin processing, and desquamatory SC enzymes, which is consistent with marked decreases in skin capacitance and NMF levels, and changes in surface topography. A recent study showed the presence of another aliphatic alcohol, 2‐propanol, between the solid keratin rods inside the corneocytes, which might explain the morphological changes induced by n‐propanol in the present study . Our hypothesis that reductions in NMF levels might be associated with skin barrier damage is consistent with the significant inverse correlation of NMF levels with the DTI as a measure of the corneocyte surface topography.…”

“…AU, arbitrary units morphological changes induced by n-propanol in the present study. 31 Our hypothesis that reductions in NMF levels might be associated with skin barrier damage is consistent with the significant inverse correlation of NMF levels with the DTI as a measure of the corneocyte surface topography. All irritants, except for AcA, induced a significant increase in the DTI, and changes such as thinning of fibres, wrinkles and elongated spots were observed as early as 24 hours after initial exposure to n-propanol and SLS.…”

Coexistence of lipid phases stabilizes interstitial water in the outer layer of mammalian skin

“…These results show that the ability of the skin's lipids to appear both in "solid" and "liquid" states (Bouwstra et al, 2001;Pham et al, 2017) explains the simultaneous presence of multiple permeability pathways for distinct chemical species.…”

“…Circumventing its function in a controlled manner has allowed for the transdermal delivery of drugs to treat a broad range of medical conditions (Hirvonen et al, 1996). There is a demonstrated need to further understand the skin's permeability mechanisms, which can be measured quantitatively (Pham et al, 2017) but not spatially resolved at the molecular level. Cells in the SC, called corneocytes, are almost entirely made up by a solid keratin mesh with water amounting to less than 50% of their dry weight (Caspers et al, 2001).…”

“…To explain the LPP, a trilayer or "sandwich" model has been proposed (Beddoes et al, 2018;Bouwstra et al, 2001;Mojumdar et al, 2015a), wherein two liquid-ordered bilayers are thought to enclose a central liquid-disordered layer through which permeation may occur. NMR experiments also showed that the skin lipids are in equilibrium between "solid" and "liquid" states, with the "solid" state being dominant (Pham et al, 2017). Due to the long times (several hours) required for the LPP to emerge in synthetic samples, it is currently not possible to use computation to quantify the relative stability of each phase.…”