Location and partition coefficients of anti-inflammatory drugs in EPC liposomes. A fluorescence quenching study using n-(9-anthroyloxy)-stearic probes

Steady-state fluorescence quenching of a series of n-(9-anthroyloxy) steari c acids (n-AS, n = 2, 6, 9 and 12) was used to investigate the location of two anti-inflammatory drugs, namely indomethacin and acemetacin, in multila mellar and unilamellar egg phosphatidylcholine liposomes (EPC) at two pH va lues (7.4 and 5.0). The quenching properties were also used in determining quantitatively the partition coefficient of both drugs in multilamellar and unilamellar EPC vesicles, at pH 7.4 using a 12-AS probe. All n-AS probes w ere quenched by both drugs and the relative quenching efficiencies are in t he order 2-AS < 6-AS < 9-AS < 12-AS. At pH 5.0, the apparent Stern-Volmer c onstant values, k(q)(app), were always higher than those obtained at pH 7.4 . The partition coefficients determined at pH 7.4 lead q to higher values f or acemetacin than for indomethacin, especially for multilamellar liposomes (MLVs) and are identical, within experimental error, to those obtained by other methods. The observation that the k app values q increase with the de pth of the probe (larger n) for both drugs at pH 7.4 suggests that the anti -inflammatory drugs can reach the inner part of the bilayer, probably with the negative carboxyl group anchored near the choline of the phospholipid h eadgroup, and with the rest of the molecule buried deeply in the membrane a nd aligned with the phospholipid aliphatic tails. Quenching of 12-AS is lar ger in MLVs than in LUVs, which can be related to the different packing of the lipids in these structures, and also to the different drug penetrations in the bilayer. (C) 2001 Elsevier Science BN. All rights reserved.