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Author:
Boija, Elisabet (Uppsala University, Department of Biochemistry)
Title:
Partitioning of Drugs and Lignin Precursor Models into Artificial Membranes
Department:
Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Biochemistry
Publication type:
Doctoral thesis, comprehensive summary (Other academic)
Language:
English
Place of publ.:
Uppsala
Publisher:
Acta Universitatis Upsaliensis
Pages:
53
Series:
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214; 207
Year of publ.:
2006
URI:
urn:nbn:se:uu:diva-7098
Permanent link:
http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7098
ISBN:
91-554-6628-1
Keywords(en) :
Biochemistry, Bilayer disk, Capillary electrophoresis, Detergent, Drug, Electrostatic interaction, Hydrophobic interaction, Immobilized liposome chromatography, Lignin, Lignin precursor model, Liposome, Membrane model, Octanol/water partitioning, Partitioning, Phospholipid, Phospholipid bilayer, Sterol
Keywords(sv) :
Biokemi
Abstract(en) :

The main aim of this thesis was to characterize membrane-solute interactions using artificial membranes in immobilized liposome chromatography or capillary electrophoresis. The partitioning of a solute into a cell membrane is an essential step in diffusion across the membrane. It is a valid parameter in drug research and can be linked to the permeability as well as the absorption of drugs. Immobilized liposome chromatography was also used to study partitioning of lignin precursor models. Lignin precursors are synthesized within plant cells and need to pass the membrane to be incorporated into lignin in the cell wall.

In immobilized liposome chromatography, liposomes or lipid bilayer disks were immobilized in gel beads and the partitioning of solutes was determined. Capillary electrophoresis using disks as a pseudostationary phase was introduced as a new approach in drug partitioning studies. In addition, octanol/water partitioning was used to determine the hydrophobicity of the lignin precursor models.

Electrostatic interactions occurred between bilayers and charged drugs, whereas neutral drugs were less affected. However, neutral lignin precursor models exhibited polar interactions. Moreover, upon changing the buffer ionic strength or the buffer ions, the interactions between charged drugs and neutral liposomes were affected. Hydrophobic interactions were also revealed by including a fatty acid or a neutral detergent into the bilayer or by using a buffer with a high salt concentration. The bilayer manipulation had only a moderate effect on drug partitioning, but the high salt concentration had a large impact on partitioning of lignin precursor models.

Upon comparing the partitioning into liposomes and disks, the latter showed a more pronounced partitioning due to the larger fraction of lipids readily available for interaction. Finally, bilayer disk capillary electrophoresis was successfully introduced for partitioning studies of charged drugs. This application will be evaluated further as an analytical partitioning method and separation technique.

Public defence:
2006-09-29, B42, BMC, Husargatan 3, Uppsala, 10:15
Degree:
degree of Doctor of Philosophy
Supervisor:
Johansson, Gunnar, Docent
Lundahl, Per, Professor
Lagerquist Hägglund, Christine, Filosofie Doktor
Opponent:
Riekkola, Marja-Liisa, Professor (Department of Chemistry, Helsinki)
Available from:
2006-09-08
Created:
2007-10-24
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