Lipid bilayers versus monolayers- Sponge phases and skin lipid domains

Katarina Ekelund

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

Sammanfattning

The L3, or sponge, phase is a thermodynamically stable isotropic liquid consisting of a surfactant membrane in aqueous solution. A solvent induced L3 phase is shown in systems of solvent, monoolein and water. Dimethyl sulfoxide, propylene glycol, polyethylene glycol, ethanol, N-methyl-alfa-pyrrolidone and 2-methyl-2,4-pentanediol are solvents of varying hydrophilicity but are all miscible with both monoolein and water. These solvents form a L3 phase with monoolein and water. It is shown that more lipophilic solvents form the L3 phase at higher level of hydration compared to more hydrophilic solvents. The L3 phase in these systems is described as a melted bicontinuous cubic phase. The phase occurs in a narrow composition range reflecting the delicate balance in keeping the slightly negative curvature of the bilayer. The amphiphilic character of the L3 phase makes it interesting as a drug vehicle for lipophilic drugs. Amphiphilic and lipophilic substances can be incorporated in the phase with knowledge of how to compensate for changes in the phase behaviour. The amphiphilic packing concept was shown to be a useful tool in predicting and compensating for changes in curvature of the monoolein bilayer. Further were some interesting possibilities of utilising the properties of the L3 phase discussed.

The main barrier for skin penetration resides in the upper layer of skin, stratum corneum, which consists of corneocytes embedded in lipid lamellar region. The intercellular region in the stratum corneum is the only continuous region and it has earlier been found that drugs and water are mainly transported through these lipid regions. Therefore, the phase behaviour of the stratum corneum lipids is of great importance for the understanding of the barrier function of the skin. The main constitutents of the stratum corneum lipids are ceramides, free fatty acids and cholesterol. A thorough investigation of the lateral organisation in a stratum corneum lipid model was undertaken. Combining atomic force microscopy (AFM) with Langmuir-Blodgett technique the two dimensional phase behaviour of two free fatty acids of different chain lengths, cholesterol and two synthetic ceramides of group III have been investigated. By studying single, binary, ternary etc mixtures and varying the composition of the monolayers the role of each lipid class was studied in detail. This study has shown large variations in size and shape of the domains depending on the molecular packing and interactions in the monolayer. Palmitic acid and lignoceric acid phase separates and form irregular shaped domains. Addition of cholesterol to the system further increases the interfacial length of the domains which can be attributed to the line active (cf. two-dimensional analogue to surface active) properties of cholesterol. Cholesterol is partial miscible with palmitic acid and the ceramides. The lipids were identified in the complex mixtures from the shape, size and difference in thickness of the different domains. Specific for the phase separated domains in ceramide-cholesterol monolayers are the very small and regular shaped domains. The size and arrangement of these domains were almost retained in more complex mixtures. This study shows a lateral heterogeneity in the mixed stratum corneum lipid monolayers.
Originalspråkengelska
KvalifikationDoktor
Tilldelande institution
  • Livsmedelsteknik
Handledare
  • [unknown], [unknown], handledare, Extern person
Tilldelningsdatum2000 mar 3
Förlag
StatusPublished - 2000

Bibliografisk information

Defence details

Date: 2000-03-03
Time: 10:15
Place: Ršda Rummet, Dept. of Ecology, Sšlvegatan 37, Lund

External reviewer(s)

Name: Lindblom, Gšran
Title: Prof
Affiliation: UmeŒ University, UmeŒ, Sweden

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Ämnesklassifikation (UKÄ)

  • Livsmedelsteknik

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