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Adsorption of a PEO-PPO-PEO triblock copolymer on small unilamellar vesicles: equilibrium and kinetic properties and correlation with membrane permeability
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.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
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2001 (English)In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 17, no 13, 3902-3911 p.Article in journal (Refereed) Published
Abstract [en]

The adsorption of the triblock copolymer F127, poly(ethylene oxide)−poly(propylene oxide)−poly(ethylene oxide), EO98PO67EO98, onto immobilized small unilamellar vesicles (SUVs) of egg phosphatidylcholine (EPC) has been studied by means of a quartz crystal microbalance (QCM). With this technique we first show that SUVs of EPC adsorb on gold to form a monolayer of vesicles. This supported monolayer of vesicles was then used to follow the adsorption of the F127 polymer onto the lipid membrane surface. The adsorption of F127 was found to be a rapid process, and the measured polymer binding isotherm was fitted to a Freundlich type of isotherm. The maximum, or plateau, adsorbed amount was determined to be of a magnitude similar to that found for adsorption of F127 on hydrophobic surfaces. Furthermore, the desorption of the triblock copolymers from the membrane surface was followed after rinsing the SUV monolayer with pure buffer. It was found that the desorption process displayed essentially the same rapid kinetics as the adsorption process, indicating a weak interaction between the polymers and the lipid membrane. The determined polymer binding isotherm was used to correlate the adsorbed amount of polymer with the polymer-induced leakage of carboxy fluorescein (CF) from the SUVs. It was found that the membrane permeability was increased severalfold already at low surface coverage and that the maximum magnitude of the CF release rate was obtained at, or close to, F127 concentrations giving rise to the maximum adsorbed amount of polymer. In addition, the increased membrane permeability induced by the triblock copolymers was compared with the effect of adding a conventional ethylene oxide (EO) surfactant, Triton X-100, to the SUVs. The result emphasizes the dramatic effect of F127 on the bilayer permeability.

Place, publisher, year, edition, pages
2001. Vol. 17, no 13, 3902-3911 p.
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:uu:diva-90316DOI: 10.1021/la0101245OAI: oai:DiVA.org:uu-90316DiVA: diva2:162626
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
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Available from: 2003-04-30 Created: 2003-04-30Bibliographically approved

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Edwards, Katarina

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