uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Partitioning of Drugs and Lignin Precursor Models into Artificial Membranes
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry.
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. , p. 53
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 207
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
Identifiers
URN: urn:nbn:se:uu:diva-7098ISBN: 91-554-6628-1 (print)OAI: oai:DiVA.org:uu-7098DiVA, id: diva2:168719
Public defence
2006-09-29, B42, BMC, Husargatan 3, Uppsala, 10:15
Opponent
Supervisors
Available from: 2006-09-08 Created: 2006-09-08 Last updated: 2011-02-17Bibliographically approved
List of papers
1. Effects of ions and detergents in drug partition chromatography on liposomes
Open this publication in new window or tab >>Effects of ions and detergents in drug partition chromatography on liposomes
Show others...
2004 In: Journal of Chromatography A, Vol. 1030, p. 273-278Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-94747 (URN)
Available from: 2006-09-08 Created: 2006-09-08Bibliographically approved
2. Interactions of drugs and an oligonucleotide with charged membranes analyzed by immobilized liposome chromatography
Open this publication in new window or tab >>Interactions of drugs and an oligonucleotide with charged membranes analyzed by immobilized liposome chromatography
Show others...
2006 In: Biomedical Chromatography, Vol. 20, p. 83-87Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-94748 (URN)
Available from: 2006-09-08 Created: 2006-09-08Bibliographically approved
3. Interactions between model membranes and lignin-related compounds studied by immobilized liposome chromatography
Open this publication in new window or tab >>Interactions between model membranes and lignin-related compounds studied by immobilized liposome chromatography
2006 (English)In: Biochimica et Biophysica Acta - Biomembranes, ISSN 0005-2736, E-ISSN 1879-2642, Vol. 1758, no 5, p. 620-626Article in journal (Refereed) Published
Abstract [en]

In order to elucidate the modes of interaction between lignin precursors and membranes, we have studied the influence of temperature, lipid composition and buffer composition on the partitioning of monolignol and dilignol model substances into phospholipid bilayers. The partitioning was determined by immobilized liposome chromatography, which is an established method for studies of pharmaceutical drugs but a new approach in studies of lignin synthesis. The temperature dependence of the retention and the effect of a high ammonium sulfate concentration in the mobile phase demonstrated that the interaction involved both hydrophobic effects and polar interactions. There was also a good correlation between the partitioning and the estimated hydrophobicity, in terms of octanol/water partitioning. The partitioning behavior of the model substances suggests that passive diffusion over the cell membrane is a possible transport route for lignin precursors. This conclusion is strengthened by comparison of the present results with the partitioning of pharmaceutical drugs that are known to pass cell membranes by diffusion.

Keywords
Lignin, liposomes, membrane, transport, plant
National Category
Biochemistry and Molecular Biology
Research subject
Biochemistry
Identifiers
urn:nbn:se:uu:diva-94749 (URN)10.1016/j.bbamem.2006.04.007 (DOI)000239102300008 ()
Available from: 2006-09-08 Created: 2006-09-08 Last updated: 2017-12-14Bibliographically approved
4. Evaluation of bilayer disks as plant cell membrane models in partition studies
Open this publication in new window or tab >>Evaluation of bilayer disks as plant cell membrane models in partition studies
2007 (English)In: Analytical Biochemistry, ISSN 0003-2697, E-ISSN 1096-0309, Vol. 364, no 2, p. 145-152Article in journal (Refereed) Published
Abstract [en]

We have studied the partitioning of a set of phenolic compounds used as lignin precursor models into lipid bilayer disks and liposomes. The bilayer disks are open bilayer structures stabilized by polyethylene glycol-conjugated lipids. Our results indicate that disks generate more accurate partition data than do liposomes. Furthermore, we show that the partitioning into the membrane phase is reduced slightly if disks composed of 1,2-distearoyl-sn-glycero-3-phosphocholine and cholesterol are exchanged for disks with a lipid composition mimicking that of the root tissue of Zea mays L.

Keywords
Immobilized liposome chromatography, Lignin, Lipid bilayer disks, Liposomes, Monolignol, Partitioning, Phenols, Plant cell membrane lipids
National Category
Chemical Sciences
Identifiers
urn:nbn:se:uu:diva-10738 (URN)10.1016/j.ab.2007.02.012 (DOI)000245960400007 ()17391634 (PubMedID)
Available from: 2008-09-01 Created: 2008-09-01 Last updated: 2017-12-11Bibliographically approved
5. Bilayer disk capillary electrophoresis: a novel method to study drug partitioning into membranes
Open this publication in new window or tab >>Bilayer disk capillary electrophoresis: a novel method to study drug partitioning into membranes
Show others...
2008 (English)In: Electrophoresis, ISSN 0173-0835, E-ISSN 1522-2683, Vol. 29, no 16, p. 3377-3383Article in journal (Refereed) Published
Abstract [en]

CE in the presence of lipid bilayer disks was introduced as a new approach in membrane partitioning studies. The disks were used as a pseudostationary phase in the partial-filling mode of CE and the partitioning of cationic drugs was determined. The migration times of the analytes increased linearly with the lipid amount in the system. An appropriate algorithm for the calculation of a partition coefficient is presented. In the disk-shaped bilayers, which have excellent stability and shelf life, all of the lipids are readily available for interaction and the disks can be used as realistic cell membrane models.

Keywords
bilayer disks, capillary electrophoresis, drugs, model membrane, partitioning
National Category
Chemical Sciences
Identifiers
urn:nbn:se:uu:diva-94751 (URN)10.1002/elps.200700682 (DOI)000258856900012 ()18702061 (PubMedID)
Available from: 2006-09-08 Created: 2006-09-08 Last updated: 2017-12-14Bibliographically approved

Open Access in DiVA

fulltext(1002 kB)1135 downloads
File information
File name FULLTEXT01.pdfFile size 1002 kBChecksum MD5
61e9e64ac1fc640444671b173da4b61aa79772038c3c8d89f8d821e0c90df9e8dfedd563
Type fulltextMimetype application/pdf
cover(564 kB)29 downloads
File information
File name COVER01.pdfFile size 564 kBChecksum MD5
a27b1e0e5362ed5d47fcdc93b4877107fd36fc42c862e39b48051513952a926f5522c048
Type coverMimetype application/pdf
Buy this publication >>

By organisation
Department of Biochemistry

Search outside of DiVA

GoogleGoogle Scholar
Total: 1135 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 1919 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf