REVIEW ARTICLE

Influence of short chain ceramides and lipophilic penetration enhancers on the nano-structure of stratum corneum model membranes studied using neutron diffraction

  • Annett SCHROETER ,
  • Tanja ENGELBRECHT ,
  • Reinhard H. H. NEUBERT
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  • Institute of Pharmacy, Martin Luther University Halle-Wittenberg, D-06120 Halle/Saale, Germany

Received date: 19 Oct 2012

Accepted date: 15 Nov 2012

Published date: 05 Mar 2013

Copyright

2014 Higher Education Press and Springer-Verlag Berlin Heidelberg

Abstract

Oriented stratum corneum model lipid membranes were used to study the influence of the short chain ceramides (CER)[NP] and [AP] as well as the impact of the lipophilic penetration enhancer molecules oleic acid (OA) and isopropyl myristate (IPM) on the lipid nanostructure. The influence of the enhancer molecules were studied using specifically deuterated OA and IPM and neutron diffraction. 2H NMR spectroscopy was used to study the impact of the ceramides’ degree of order within the stratum corneum model lipid membranes. It was found that CER[NP] forms two very stable phases with high resistance against temperature increase. Phase B showed unusual hydration behavior as no water uptake of this phase was observed. The 2H NMR spectroscopic measurements showed that CER[NP] based ternary model system had a higher state of lamellar order in comparison to CER[AP] based lipid matrix.

The studies confirmed that the short chain ceramides, particularly CER[NP], have a very high impact on the integrity of the Stratum corneum lipid bilayers. The penetration enhancer OA has not influenced the repeat distance of the model membrane based on CER[AP], and was not able to induce a phase separation in the investigated lipid matrix. However, a disorder and a fluidisation of the model membranes were observed when OA was incorporated. IPM showed the same effect but two phases (assigned as phase A and B) appeared, when IPM was used as penetration enhancer and incorporated into the model membrane. Furthermore, two arrangements of IPM were identified in phase A using deuterated IPM. A model of the nanostructure of the Stratum corneum lipid membranes is presented.

Cite this article

Annett SCHROETER , Tanja ENGELBRECHT , Reinhard H. H. NEUBERT . Influence of short chain ceramides and lipophilic penetration enhancers on the nano-structure of stratum corneum model membranes studied using neutron diffraction[J]. Frontiers of Chemical Science and Engineering, 2013 , 7(1) : 29 -36 . DOI: 10.1007/s11705-013-1302-0

1
Kessner D, Kiselev M A, Dante S, Hauss T, Lersch P, Wartewig S, Neubert R H H. Arrangement of ceramide [EOS] in a stratum corneum lipid model matrix: new aspects revealed by neutron diffraction studies. European Biophysics Journal with Biophysics Letters, 2008, 37(6): 989–999

DOI

2
Kessner D, Kiselev M A, Hauss T, Dante S, Wartewig S, Neubert R H H. Localisation of partially deuterated cholesterol in quaternary SC lipid model membranes: a neutron diffraction study. European Biophysics Journal with Biophysics Letters, 2008, 37(6): 1051–1057

DOI

3
Kiselev M A. Conformation of ceramide 6 molecules and chain-flip transitions in the lipid matrix of the outermost layer of mammalian skin, the stratum corneum. Crystallography Reports, 2007, 52(3): 525–528

DOI

4
Kiselev M A, Ryabova N Y, Balagurov A M, Dante S, Hauss T, Zbytovska J, Wartewig S, Neubert R H H. New insights into the structure and hydration of a stratum corneum lipid model membrane by neutron diffraction. European Biophysics Journal, 2005, 34(8): 1030–1040

DOI

5
Wegener M, Neubert R H H, Rettig W, Wartewig S. Structure of stratum corneum lipids characterized by FT-Raman spectroscopy and DSC. III. Mixtures of ceramides and cholesterol. Chemistry and Physics of Lipids, 1997, 88(1): 73–82

DOI

6
Zbytovska J, Vavrova K, Kiselev M A, Lessieur P, Wartewig S, Neubert R H H. The effects of transdermal permeation enhancers on thermotropic phase behaviour of a stratum corneum lipid model. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2009, 351(1-3): 30–37

DOI

7
Schroeter A, Kiselev M A, Hauss T, Dante S, Neubert R H H. Evidence of free fatty acid interdigitation in stratum corneum model membranes based on ceramide [AP] by deuterium labelling. Biochimica et Biophysca Acta. Biomembranes, 2009, 1788(10): 2194

DOI

8
Engelbrecht T N, Deme B, Dobner B, Neubert R H H. Study of influence of penetration enhancer isopropylmyristate on the nanostructure of stratum corneum lipid model membranes using neutron diffraction and deuterium labelling. Skin Pharmacology and Physiology, 2012, 25(4): 200–207

DOI

9
Engelbrecht T N, Schroeter A, Hauss T, Neubert R H H. Lipophilic penetration enhancers and their impact to the bilayer structure of stratum corneum lipid model membranes: neutron diffraction studies based on the example oleic acid. Biochimica et Biophysica Acta. Biomembranes, 2011, 1808(12): 2798–2806

DOI

10
Holbrook K A, Odland G F. Regional differences in the thickness (cell layers) of the human stratum corneum: an ultrastructural analysis. Journal of Investigative Dermatology, 1974, 62(4): 415–422

DOI

11
Scheuplein R J, Morgan L J. “Bound water” in keratin membranes measured by a microbalance technique. Nature, 1967, 214(5087): 456–458

DOI

12
Loomans M E, Hannon D P. An electron microscopic study of the effects of subtilisin and detergents on human stratum corneum. Journal of Investigative Dermatology, 1970, 55(2): 101–114

DOI

13
Blank I H, Scheuplein R J. Transport into and within skin. British Journal of Dermatology, 1969, S 81: 4–10

14
Mackenzie J C. Ordered structure of the stratum corneum of mammalian skin. Nature, 1969, 222(5196): 882

DOI

15
Candi E, Schmidt R, Melino G. The cornified envelope: a model of cell death in the skin. Nature Reviews. Molecular Cell Biology, 2005, 6(4): 328–340

DOI

16
Elias P M. Epidermal lipids, barrier function, and desquamation. Journal of Investigative Dermatology, 1983, 80(1s Suppl): 44s–49s

DOI

17
Elias P M. Structure and function of the stratum-corneum permeability barrier. Drug Development Research, 1988, 13(2-3): 97–105

DOI

18
Elias P M, Friend D S. The permeability barrier in mammalian epidermis. Journal of Cell Biology, 1975, 65(1): 180–191

DOI

19
Elias P M, Goerke J, Friend D S. Mammalian epidermal barrier layer lipids–composition and influence on structure. Journal of Investigative Dermatology, 1977, 69(6): 535–546

DOI

20
Landmann L. The epidermal permeability barrier. Anatomy and Embryology, 1988, 178(1): 1–13

DOI

21
El Maghraby G M, Barry B W, Williams A C. Liposomes and skin: from drug delivery to model membranes. European Journal of Pharmaceutical Sciences, 2008, 34(4-5): 203–222

DOI

22
Gray G, Yardley H. Different populations of pig epidermal-cells–isolation and lipid composition. Journal of Lipid Research, 1975, 16(6): 441–447

23
Gray G, Yardley H. Lipid compositions of cells isolated from pig, human, and rat epidermis. Journal of Lipid Research, 1975, 16(6): 434–440

24
Wertz P W, van den Bergh B. The physical, chemical and functional properties of lipids in the skin and other biological barriers. Chemistry and Physics of Lipids, 1998, 91(2): 85–96

DOI

25
Law S L, Wertz P W, Swartzendruber S C A, Squier C A. Regional variation in content, composition and organization of porcine epithelial barrier lipids revealed by thin-layer chromatography and transmission electron microscopy. Archives of Oral Biology, 1995, 40(12): 1085–1091

DOI

26
Di Nardo A, Wertz P, Giannetti A, Seidenari S. Ceramide and cholesterol composition of the skin of patients with atopic dermatitis. Acta Dermato-Venereologica, 1998, 78(1): 27–30

DOI

27
Motta S, Monti M, Sesana S, Mellesi L, Ghidoni R, Caputo R. Abnormality of water barrier function in psoriasis. Role of ceramide fractions. Archives of Dermatology, 1994, 130(4): 452–456

DOI

28
Madison K C, Swartzendruber D C, Wertz P W, Downing D T. Presence of intact intercellular lipid lamellae in the upper layers of the stratum corneum. Journal of Investigative Dermatology, 1987, 88(6): 714–718

DOI

29
Swartzendruber D C, Wertz P W, Kitko D J, Madison K C, Downing D T. Molecular models of the intercellular lipid lamellae in mammalian stratum corneum. Journal of Investigative Dermatology, 1989, 92(2): 251–257

DOI

30
Forslind B. A domain mosaic model of the skin barrier. Acta Dermato-Venereologica, 1994, 74(1): 1–6

31
Bouwstra J A, Gooris G S, van der Spek J A, Bras W. Structural investigations of human stratum corneum by small-angle X-ray scattering. Journal of Investigative Dermatology, 1991, 97(6): 1005–1012

DOI

32
Bouwstra J A, Dubbelaar F E, Gooris G S, Ponec M. The lipid organisation in the skin barrier. Acta Dermato-Venereologica. Supplementum, 2000, 208(Suppl): 23–30

33
White S H, Mirejovsky D, King G I. Structure of lamellar lipid domains and corneocyte envelopes of murine stratum corneum. An X-ray diffraction study. Biochemistry, 1988, 27(10): 3725–3732

DOI

34
Iwai I, Han H, Hollander L D, Svensson S, Ofverstedt L G, Anwar J, Brewer J, Bloksgaard M, Laloeuf A, Nosek D, Masich S, Bagatolli L A, Skoglund U, Norlen L. The human skin barrier is organized as stacked bilayers of fully extended ceramides with cholesterol molecules associated with the ceramide sphingoid moiety. Journal of Investigative Dermatology, 2012, 132(9): 2215–2225

DOI

35
Trommer H, Neubert R H H. Overcoming the stratum corneum: The modulation of skin penetration–a review. Skin Pharmacology and Physiology, 2006, 19(2): 106–121

DOI

36
Barry B W. Mode of action of penetration enhancers in human skin. Journal of Controlled Release, 1991, 15(3): 237–248

DOI

37
Nagle J F, Tristram-Nagle S. Structure of lipid bilayers. Biochimica et Biophysica Acta, 2000, 1469(3): 159–195

DOI

38
Seul M, Sammon M J. Reparation of surfactant multilayer films on solid substrates by deposition from organic solution. Thin Solid Films, 1990, 185(2): 287–305

DOI

39
Rowat A C, Kitson N, Thewalt J L. Interactions of oleic acid and model stratum corneum membranes as seen by 2H NMR. International Journal of Pharmaceutics, 2006, 307(2): 225–231

DOI

40
Sternin E, Bloom M, Mackay A L. De-pakeing of NMR spectra. Journal of Magnetic Resonance (San Diego, Calif.), 1983, 55(2): 274–282

41
Davis J H, Jeffrey K R, Bloom M, Valic M I, Higgs T P. Quadrupolar echo deuteron magnetic resonance spectroscopy in ordered hydrocarbon chains. Chemical Physics Letters, 1976, 42(2): 390–394

DOI

42
Davis J H, Jeffrey K R. Temperature dependence of chain disorder in potassium palmitate-water –A deuterium NMR study. Chemistry and Physics of Lipids, 1977, 20(2): 87–104

DOI

43
Takeuchi Y, Yamaoka Y, Fukushima S, Miyawaki K, Taguchi K, Yasukawa H, Kishimoto S, Suzuki M. Skin penetration enhancing action of cis-unsaturated fatty acids with omega-9, and omega-12-chain lengths. Biological & Pharmaceutical Bulletin, 1998, 21(5): 484–491

DOI

44
Tonegawa A, Michiue A, Masuda T, Ohno T, Matsuura H, Yamada K, Okuda T. Deuterium NMR and Raman spectroscopic studies on conformational behavior of lipophilic chains in the C12E3/decane/water system. Zeitschrift für Naturforschung A–A Journal of Physical Sciences, 2002, 57(6-7): 320–326

45
Engelbrecht T N, Schroeter A, Hauss T, Deme B, Scheidt H A, Huster D, Neubert R H H. The impact of ceramides NP and AP to nanostructure of stratum corneum lipid model membranes. Part I: Neutron diffraction and 2H NMR studies on multilamellar models based on ceramides with symmetric alkyl chain length distribution. Soft Matter, 2012, 8(24): 6599–6607

DOI

46
Engelbrecht T N, Hauss T, Suss K, Vogel A, Roark M, Feller S E, Neubert R H H, Dobner B. Characterisation of a new ceramide EOS species: Synthesis, investigation of the thermotropicphase behaviour and influence on the bilayer architecture of stratum corneum lipid model membranes. Soft Matter, 2011, 7(19): 8998–9011

DOI

47
Mitriaikina S, Muller-Goymann C C. Synergetic effects of isopropyl alcohol (IPA) and isopropyl myristate (IPM) on the permeation of betamethasone-17-valerate from semisolid Pharmacopoeia bases. Journal of Drug Delivery Science and Technology, 2007, 17(5): 339–346

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