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Interactions of drugs and an oligonucleotide with charged membranes analyzed by immobilized liposome chromatography
Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Biochemistry.
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2006 In: Biomedical Chromatography, Vol. 20, 83-87 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2006. Vol. 20, 83-87 p.
URN: urn:nbn:se:uu:diva-94748OAI: oai:DiVA.org:uu-94748DiVA: diva2:168715
Available from: 2006-09-08 Created: 2006-09-08Bibliographically approved
In thesis
1. Partitioning of Drugs and Lignin Precursor Models into Artificial Membranes
Open this publication in new window or tab >>Partitioning of Drugs and Lignin Precursor Models into Artificial Membranes
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
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.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2006. 53 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 207
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, Biokemi
urn:nbn:se:uu:diva-7098 (URN)91-554-6628-1 (ISBN)
Public defence
2006-09-29, B42, BMC, Husargatan 3, Uppsala, 10:15
Available from: 2006-09-08 Created: 2006-09-08 Last updated: 2011-02-17Bibliographically approved

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