title: Influence of the penetration enhancer isopropyl myristate on stratum corneum lipid model membranes revealed by neutron diffraction and2H NMR experiments.
abstract: The stratum corneum (SC) provides the main barrier properties in native skin. The barrier function is attributed to the intercellular lipids, forming continuous multilamellar membranes. In this study, SC lipid membranes in model ratios were enriched with deuterated lipids in order to investigate structural and dynamical properties by neutron diffraction and2H solid-state NMR spectroscopy. Further, the effect of the penetration enhancer isopropyl myristate (IPM) on the structure of a well-known SC lipid model membrane containing synthetically derived methyl-branched ceramide [EOS], ceramide [AP], behenic acid and cholesterol (23/10/33/33wt%) was investigated. IPM supported the formation of a single short-periodicity phase (SPP), in which we determined the molecular organization of CER[AP] and CER[EOS]-br for the first time. Furthermore, the thermotropic phase behavior of the lipid system was analyzed by additional neutron diffraction studies as well as by2H solid-state NMR spectroscopy, covering temperatures of 32°C (physiological skin temperature), 50°C, and 70°C with a subsequent cooldown back to skin temperature. Both techniques revealed a phase transition and a hysteresis effect. During the cooldown, Bragg peaks corresponding to a long-periodicity phase (LPP) appeared. Additionally,2H NMR revealed that the IPM molecules are isotopic mobile at all temperatures.
authors.affiliation: Institute of Pharmacy, Martin Luther University Halle-Wittenberg, 06120 Halle/Saale, Germany.
authors.forename: Adina
authors.initials: A
authors.lastname: Eichner
authors.affiliation: Institute of Medical Physics and Biophysics, University of Leipzig, 04107 Leipzig, Germany.
authors.forename: Sören
authors.initials: S
authors.lastname: Stahlberg
authors.affiliation: Institute of Pharmacy, Martin Luther University Halle-Wittenberg, 06120 Halle/Saale, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Sonnenberger
authors.affiliation: Institute of Pharmacy, Martin Luther University Halle-Wittenberg, 06120 Halle/Saale, Germany; Institute of Medical Physics and Biophysics, University of Leipzig, 04107 Leipzig, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Lange
authors.affiliation: Institute of Pharmacy, Martin Luther University Halle-Wittenberg, 06120 Halle/Saale, Germany.
authors.forename: Bodo
authors.initials: B
authors.lastname: Dobner
authors.affiliation: Heinz Maier-Leibnitz Zentrum (MLZ), Technische Universität München, 85748 Garching, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Ostermann
authors.affiliation: Jülich Centre for Neutron Science (JCNS) at Heinz Maier-Leibnitz Zentrum (MLZ), Forschungszentrum Jülich GmbH, 85748 Garching, Germany.
authors.forename: Tobias E
authors.initials: TE
authors.lastname: Schrader
authors.affiliation: Institute of Soft Matter and Functional Materials, Helmholtz-Zentrum Berlin für Materialien und Energie, 14109 Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hauß
authors.affiliation: Institute of Pharmacy, Martin Luther University Halle-Wittenberg, 06120 Halle/Saale, Germany.
authors.forename: Annett
authors.initials: A
authors.lastname: Schroeter
authors.affiliation: Institute of Medical Physics and Biophysics, University of Leipzig, 04107 Leipzig, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Huster
authors.affiliation: Institute of Pharmacy, Martin Luther University Halle-Wittenberg, 06120 Halle/Saale, Germany; Institute of Applied Dermatopharmacy at the Martin Luther University Halle-Wittenberg, 06120 Halle/Saale, Germany. Electronic address: reinhard.neubert@pharmazie.uni-halle.de.
authors.forename: Reinhard H H
authors.initials: RH
authors.lastname: Neubert
mesh_terms: D002518:Ceramides / Q000737:chemistry; D004817:Epidermis / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D009226:Myristates / Q000494:pharmacology*; D033363:Neutron Diffraction / Q000379:methods*; D044367:Phase Transition; D012881:Skin Temperature
chemical_list: D002518:Ceramides; D008051:Lipid Bilayers; D009226:Myristates; C008205:isopropyl myristate
keywords: (2)H solid-state NMR spectroscopy; Ceramides; Lipid model membranes; Long-periodicity phase; Neutron diffraction; Penetration enhancer; Phase transition; Short-periodicity phase; Stratum corneum