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Aggregate structure in dilute aqueous dispersions of phospholipids, fatty acids and lysophospholipids
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
2001 (English)In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 17, no 11, 3245-3253 p.Article in journal (Refereed) Published
Abstract [en]

Cryo-transmission electron microscopy (cryo-TEM) was employed to investigate the aggregate structure in dilute aqueous dispersions of egg-phosphatidylcholine (EPC), oleic acid (OA), and the lysophospholipid monooleoylphosphatidylcholine (MOPC). At physiological pH and salt concentration, a relatively monodisperse population of unilamellar liposomes was detected in mixtures containing equimolar concentrations of the three components. Threadlike micelles constituted the dominant aggregate structure in samples containing high concentrations of MOPC. Excess fatty acid forced, on the other hand, the system toward structures with net negative curvature. In the absence of phospholipid, cryo-TEM revealed bilayer fragments in coexistence with threadlike micelles in mixtures containing the same molar amount of MOPC and OA. External addition of MOPC to preformed EPC liposomes gave rise to a concentration dependent evolution of intermediate structures, including open liposomes and bilayer fragments. The structural rearrangements were found to be slow and permitted visualization of a number of interesting transition structures. In addition to the structural studies, static and time-resolved fluorescence measurements were employed to determine some fundamental parameters for MOPC micelles. The results indicate a critical micelle concentration of close to 5 μM and an aggregation number of approximately 142.

Place, publisher, year, edition, pages
2001. Vol. 17, no 11, 3245-3253 p.
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:uu:diva-90315DOI: 10.1021/la010020uOAI: oai:DiVA.org:uu-90315DiVA: diva2:162625
Available from: 2003-04-30 Created: 2003-04-30 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Liposomes for Drug Delivery: from Physico-chemical Studies to Applications
Open this publication in new window or tab >>Liposomes for Drug Delivery: from Physico-chemical Studies to Applications
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Physico-chemical characterisation of structure and stability of liposomes intended for drug delivery is the central issue in this thesis. In addition, targeted liposomes to be used in boron neutron capture therapy (BNCT) were developed.

Lysolipids and fatty acids are products formed upon hydrolysis of PC-lipids. The aggregate structure formed upon mixing lysolipids, fatty acids and EPC were characterised by means of cryo-TEM. A relatively monodisperse population of unilamellar liposomes was detected in mixtures containing equimolar concentration of the three components.

The interactions between alternative steric stabilisers (PEO-PPO-PEO copolymers) and conventional PC-and pH-sensitive PE-liposomes were investigated. Whereas the PE-liposomes could be stabilised by the PEO-PPO-PEO copolymers, the PC-liposomes showed an enhanced permeability concomitant with the PEO-PPO-PEO adsorption.

Permeability effects induced by different PEG-stabilisers on EPC liposomes were shown to be dependent on the length of the PEG chain but also on the linkage used to connect the PEG polymer with the hydrophobic membrane anchor.

An efficient drug delivery requires, in most cases, an accumulation of the drug in the cell cytoplasm. The mechanism behind cytosolic drug delivery from pH-sensitive liposomes was investigated. The results suggest that a destabilisation of the endosome membrane, due to an incorporation of non-lamellar forming lipids, may allow the drug to be released.

Furthermore, sterically stabilised liposomes intended for targeted BNCT have been characterised and optimised concerning loading and retention of boronated drugs.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2003. 71 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1104-232X ; 826
Keyword
Physical chemistry, liposome, steric stabilisation, BNCT, cryo-TEM, EGF, targeting, stability, permeability, pH-sensitive liposomes, triggered release, Fysikalisk kemi
National Category
Physical Chemistry
Research subject
Physical Chemistry
Identifiers
urn:nbn:se:uu:diva-3390 (URN)91-554-5592-1 (ISBN)
Public defence
2003-05-23, B41, BMC, Uppsala, 10:15
Opponent
Supervisors
Available from: 2003-04-30 Created: 2003-04-30Bibliographically approved

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Edwards, Katarina

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