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Partition and location of nimesulide in EPC liposomes: a spectrophotometric and fluorescence study

Title
Partition and location of nimesulide in EPC liposomes: a spectrophotometric and fluorescence study
Type
Article in International Scientific Journal
Year
2003
Authors
Ferreira, H
(Author)
Other
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Lucio, M
(Author)
Other
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de Castro, B
(Author)
FCUP
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Gameiro, P
(Author)
FCUP
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Reis, S
(Author)
FFUP
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Journal
Vol. 377 No. 2
Pages: 293-298
ISSN: 1618-2642
Publisher: Springer Nature
Indexing
Scientific classification
FOS: Natural sciences > Chemical sciences
CORDIS: Health sciences
Other information
Authenticus ID: P-000-F6X
Resumo (PT): Study of the mechanism of action of anti-inflammatory drugs (NSAIDs) and their side-effects may fall in the domain of membranology. In this work the extent of the interaction between an NSAID (nimesulide) and membrane phospholipids was quantified by the partition coefficient, Kp , using egg phosphatidylcholine (EPC) liposomes as cell membrane models. The liposome/aqueous phase partition coefficients were determined under physiological conditions, by derivative spectrophotometry and fluorescence quenching. Derivative spectrophotometry allows elimination of background signal effects (light scattering) due to the presence of liposomes. Theoretical models, accounting for simple partition of the NSAID between two different media, were used to fit the experimental data, allowing the determination of Kp in multilamellar vesicles (MLVs) and large unilamellar vesicles (LUVs). The location of nimesulide in MLVs and LUVs was evaluated by fluorescence quenching using spectroscopic probes located at different sites on the membrane. All n-AS probes were quenched and the relative quenching efficiencies were ordered as 2-AS<6-AS9-AS<12-AS; this suggests the drug is deeply buried in the membrane. Fluorescence quenching using the 12-AS probe was also used to determine the partition coefficient of the drug in MLVs and LUVs. The two techniques yield similar results. Finally, measurement of zeta-potential in the presence of different concentrations of nimesulide was performed to investigate possible changes in the zwitterionic phosphatidylcholine membranes. The membrane surface potential was not altered, which seems to be an indication that nimesulide binds to lipid bilayer mostly by hydrophobic interactions. <br> <br> Keywords Partition coefficient - Nimesulide - Liposomes - Derivative spectrophotometry - Fluorescence quenching <br> <a target="_blank" href="http://www.springerlink.com/content/6nmuyxfemvclv5jb/?p=014fb37f6a814577ace255dc4410d5ec&pi=11"> Texto integral</a> <br> <br>
Abstract (EN): Study of the mechanism of action of anti-inflammatory drugs (NSAIDs) and their side-effects may fall in the domain of membranology. In this work the extent of the interaction between an NSAID (nimesulide) and membrane phospholipids was quantified by the partition coefficient, K-p , using egg phosphatidylcholine (EPC) liposomes as cell membrane models. The liposome/aqueous phase partition coefficients were determined under physiological conditions, by derivative spectrophotometry and fluorescence quenching. Derivative spectrophotometry allows elimination of background signal effects (light scattering) due to the presence of liposomes. Theoretical models, accounting for simple partition of the NSAID between two different media, were used to fit the experimental data, allowing the determination of K-p in multilamellar vesicles (MLVs) and large unilamellar vesicles (LUVs). The location of nimesulide in MLVs and LUVs was evaluated by fluorescence quenching using spectroscopic probes located at different sites on the membrane. All n-AS probes were quenched and the relative quenching efficiencies were ordered as 2-AS<6-ASapproximate to9-AS<12-AS; this suggests the drug is deeply buried in the membrane. Fluorescence quenching using the 12-AS probe was also used to determine the partition coefficient of the drug in MLVs and LUVs. The two techniques yield similar results. Finally, measurement of zeta-potential in the presence of different concentrations of nimesulide was performed to investigate possible changes in the zwitterionic phosphatidylcholine membranes. The membrane surface potential was not altered, which seems to be an indication that nimesulide binds to lipid bilayer mostly by hydrophobic interactions.
Language: English
Type (Professor's evaluation): Scientific
No. of pages: 6
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