Effects of diclofenac on EPC liposome membrane properties.
In this work the interaction of a non-steroidal anti-inflammatory drug (NSAID), diclofenac, with egg yolk phosphatidylcoline (EPC) liposomes, used as cell-membrane models, was quantified by determination of the partition coefficient. The liposome/aqueous phase partition coefficient was determined by derivative spectrophotometry, fluorescence quenching, and measurement of zeta-potential. Theoretical models based on simple partition of the diclofenac between two different media, were used to fit the experimental data, enabling the determination of K(p). The three techniques used yielded similar results. The effects of the interaction on the membrane's characteristics were further evaluated, either by studying membrane potential changes or by effects on membrane fluidity. The liposome membrane potential and the size and size-homogeneity of liposomes were measured by light scattering. The effects of diclofenac on the internal viscosity or fluidity of the membrane were determined by use of spectroscopic probes-a series of n-(9-anthroyloxy) fatty acids in which the carboxyl terminal group is located at the interfacial region of the membrane and the fluorescent anthracene group is attached at different positions along the fatty acid chain. The location of the diclofenac on the membrane was also evaluated, by fluorescence quenching using the same series of fluorescent probes. Because the fluorescent anthracene group is attached at different positions along the fatty acid chain, it is possible to label at a graded series of depths in the bilayer. The interactions between the drug and the probe are a means of predicting the location of the drug on the membrane.
Ferreira
Helena
H
REQUIMTE/Dep. de Química-Física, Faculdade de Farmácia, Universidade do Porto, Rua Aníbal Cunha 164, 4050-047, Porto, Portugal.
Lúcio
Marlene
M
Lima
José L F C
JL
Matos
Carla
C
Reis
Salette
S
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000494:pharmacology; D004008:Diclofenac / Q000737:chemistry* / Q000494:pharmacology; D004530:Egg Yolk / Q000737:chemistry*; D005454:Fluorescence Polarization; D006863:Hydrogen-Ion Concentration; D008081:Liposomes; D008560:Membrane Fluidity / Q000187:drug effects; D008564:Membrane Potentials; D008954:Models, Biological; D010713:Phosphatidylcholines / Q000737:chemistry*; D013053:Spectrophotometry
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008081:Liposomes; D010713:Phosphatidylcholines; D004008:Diclofenac