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On the Phase Behaviour of Lipids with Respect to Skin Barrier Function

Engblom, Johan (1996)
Abstract
The aim of this thesis has been to provide further understanding of skin barrier function from a chemical point of view. The main barrier is known to be located in the outermost layer of the skin, stratum corneum, composed of cornified flattened cells in conjunction with an extracellular lipid-water matrix. From literature it is evident that the lipids of this matrix are arranged as bilayers, aligned parallel to the skin surface, preventing penetration of both polar and non-polar substances. However, the complex mixture of significantly different lipids in skin implies phase-separation to be reasonable expectation. The well-known penetration enhancer Azone® (laurocapram) was used to study the effects on lipid morphology and any... (More)
The aim of this thesis has been to provide further understanding of skin barrier function from a chemical point of view. The main barrier is known to be located in the outermost layer of the skin, stratum corneum, composed of cornified flattened cells in conjunction with an extracellular lipid-water matrix. From literature it is evident that the lipids of this matrix are arranged as bilayers, aligned parallel to the skin surface, preventing penetration of both polar and non-polar substances. However, the complex mixture of significantly different lipids in skin implies phase-separation to be reasonable expectation. The well-known penetration enhancer Azone® (laurocapram) was used to study the effects on lipid morphology and any transformation into non-lamellar structures was believed to reflect a higher permeability of polar and/or non-polar substances. Azone was added to several different lipid-water systems, some of them chosen because they are previously well characterised while others show a closer resemblance to the actual lipid composition of stratum corneum. The fatty acid and the fatty acid-cholesterol systems showed multiple phase co-existence at body temperature and below. The effects observed from adding penetration enhancers like azone were formation of reversed types of phases in liquid crystals and phase separation into a separate oil phase and water-enriched phases, due to the ability of azone to dissolve protonated fatty acids as well as cholesterol. The presence of cholesterol in fatty acid-soap-water mixtures maintained the lamellar liquid crystal, while azone caused a swelling of the bilayer to a certain level. Azone was observed to solubilize gel phases, but no significant effect on the crystals in pure fatty acid-soap-water mixtures was observed. A thorough investigation on the swelling behaviour of bicontinuous lyotropic mesophases was undertaken and the theory obtained here was applied to SAXD-data from the glycerol monooleate (GMO)-water system, containing azone. The obtained results indicate about 19% of the weakly polar, and water immiscible, azone to be anchored at the lipid-water interface. This corresponds to an effective surfactant parameter, cpp, of azone well over one (i.e. azone clearly favours reversed types of phases in liquid crystals). These observations clearly indicate that one reason for the enhanced permeability through skin of several substances by adding azone (or other substances such as oleic acid) may be the formation of non-lamellar structures in the extracellular lipid matrix. In addition, the occurrence of multiple phases, both liquid crystalline and gel/crystalline, support the idea of the matrix being non-homogeneous in lipid composition. Phase co-existence has also been observed in skin lipids and in stratum corneum in vitro by others. This domain mosaic organisation of the lipids would also contribute to the barrier efficiency. (Less)
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author
opponent
  • Prof. Kitson, Neil, Division of Dermatology, University of British Columbia, Vancouver, Canada
publishing date
type
Thesis
publication status
published
subject
keywords
glycerol monooleate, cholesterol, fatty acids, azone, bicontinuous mesophases, phase behaviour, lipid polymorphism, Stratum corneum, skin penetration, X-ray, Food and drink technology, Livsmedelsteknik
pages
70 pages
publisher
Food Technology, Engineering and Nutrition, Lund University
defense location
Chemical Centre (Room G), Lund
defense date
1996-05-15 10:15
external identifiers
  • Other:LUTKDH/TKL0-1026/1-70
language
English
LU publication?
no
id
f48ceb3d-a7f8-4a07-ac3d-87ff26b97cda (old id 28414)
date added to LUP
2007-06-12 10:48:46
date last changed
2016-09-19 08:45:11
@phdthesis{f48ceb3d-a7f8-4a07-ac3d-87ff26b97cda,
  abstract     = {The aim of this thesis has been to provide further understanding of skin barrier function from a chemical point of view. The main barrier is known to be located in the outermost layer of the skin, stratum corneum, composed of cornified flattened cells in conjunction with an extracellular lipid-water matrix. From literature it is evident that the lipids of this matrix are arranged as bilayers, aligned parallel to the skin surface, preventing penetration of both polar and non-polar substances. However, the complex mixture of significantly different lipids in skin implies phase-separation to be reasonable expectation. The well-known penetration enhancer Azone® (laurocapram) was used to study the effects on lipid morphology and any transformation into non-lamellar structures was believed to reflect a higher permeability of polar and/or non-polar substances. Azone was added to several different lipid-water systems, some of them chosen because they are previously well characterised while others show a closer resemblance to the actual lipid composition of stratum corneum. The fatty acid and the fatty acid-cholesterol systems showed multiple phase co-existence at body temperature and below. The effects observed from adding penetration enhancers like azone were formation of reversed types of phases in liquid crystals and phase separation into a separate oil phase and water-enriched phases, due to the ability of azone to dissolve protonated fatty acids as well as cholesterol. The presence of cholesterol in fatty acid-soap-water mixtures maintained the lamellar liquid crystal, while azone caused a swelling of the bilayer to a certain level. Azone was observed to solubilize gel phases, but no significant effect on the crystals in pure fatty acid-soap-water mixtures was observed. A thorough investigation on the swelling behaviour of bicontinuous lyotropic mesophases was undertaken and the theory obtained here was applied to SAXD-data from the glycerol monooleate (GMO)-water system, containing azone. The obtained results indicate about 19% of the weakly polar, and water immiscible, azone to be anchored at the lipid-water interface. This corresponds to an effective surfactant parameter, cpp, of azone well over one (i.e. azone clearly favours reversed types of phases in liquid crystals). These observations clearly indicate that one reason for the enhanced permeability through skin of several substances by adding azone (or other substances such as oleic acid) may be the formation of non-lamellar structures in the extracellular lipid matrix. In addition, the occurrence of multiple phases, both liquid crystalline and gel/crystalline, support the idea of the matrix being non-homogeneous in lipid composition. Phase co-existence has also been observed in skin lipids and in stratum corneum in vitro by others. This domain mosaic organisation of the lipids would also contribute to the barrier efficiency.},
  author       = {Engblom, Johan},
  keyword      = {glycerol monooleate,cholesterol,fatty acids,azone,bicontinuous mesophases,phase behaviour,lipid polymorphism,Stratum corneum,skin penetration,X-ray,Food and drink technology,Livsmedelsteknik},
  language     = {eng},
  pages        = {70},
  publisher    = {Food Technology, Engineering and Nutrition, Lund University},
  title        = {On the Phase Behaviour of Lipids with Respect to Skin Barrier Function},
  year         = {1996},
}