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

• Tipo: Artigo em Revista Científica Internacional
• Data: 2003

Autores

Ferreira, H (Autor) Outra; Lucio, M (Autor) Outra; de Castro, B (Autor) FCUP; Gameiro, P (Autor) FCUP; Lima, JLFC (Autor) FFUP; Reis, S (Autor) FFUP

Revista

Título: Analytical and Bioanalytical Chemistry

Vol. 377 Nº 2

Páginas: 293-298

ISSN: 1618-2642

Editora: Springer Nature

Indexação

ISI Web of Knowledge - 48 Citações

ISI Web of Science

Scopus - 50 Citações

Classificação Científica

FOS: Ciências exactas e naturais > Química

CORDIS: Ciências da Saúde

Outras Informações

ID Authenticus: P-000-F6X

DOI: 10.1007/s00216-003-2089-5

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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 6