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 ( @entity9695 ) and membrane phospholipids was quantified by the partition coefficient, K(p ), using egg @entity2434 (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 @entity5222 ( @entity5222 ) and large unilamellar vesicles (LUVs). The location of @entity9695 in @entity5222 and LUVs was evaluated by fluorescence quenching using spectroscopic probes located at different sites on the membrane. All n- @entity5427 probes were quenched and the relative quenching efficiencies were ordered as 2- @entity5427 <6- @entity5427 approximately 9- @entity5427 <12- @entity5427 ; this suggests the drug is deeply buried in the membrane. Fluorescence quenching using the 12- @entity5427 probe was also used to determine the partition coefficient of the drug in @entity5222 and LUVs. The two techniques yield similar results. Finally, measurement of zeta-potential in the presence of different concentrations of @entity9695 was performed to investigate possible changes in the zwitterionic @entity2434 membranes. The membrane surface potential was not altered, which seems to be an indication that @entity9695 binds to lipid bilayer mostly by hydrophobic interactions.

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

@entity5222 :: ('MESH:C567751', 'Disease') :: ['MLVs', 'multilamellar vesicles'] @entity9695 :: ('MESH:C012655', 'Chemical') :: ['nimesulide'] @entity2434 :: ('MESH:D010713', 'Chemical') :: ['phosphatidylcholine'] @entity5427 :: ('MESH:D017204', 'Disease') :: ['AS']
@entity9695 :: (MESH:C012655,Chemical) :: ['nimesulide']
