An NMR and DSC study of the interaction of phospholipid vesicles with some anti-inflammatory agents

Interactions of vesicles of dipalmitoyl phosphatidylcholine with the anti-inflammatory agents sulindac sulfide, naproxen, phenylbutazone, and indomethacin and the structurally related physiologically inactive compounds sulindac, sulindac sulfone, and 5-methoxy-2-methyl-indole-3-acetic acid were studied by differential scanning calorimetry and by the measurement of nuclear Overhauser effects (NOEs), using 1D- and 2D-NMR methods. Coefficients P, indicating the partition of a guest compound between the vesicle and the water phase, were calculated from DSC data. For the potent agents sulindac sulfide and indomethacin high P values were found, the less active agents naproxen and phenylbutazone had lower P values, and the inactive compounds were only slightly incorporated into the bilayers. 2D-NOE spectra for most of the guest compounds show intermolecular interactions indicating that at least part of the molecules interacting with the vesicle walls are included in the alkyl chain area of the bilayer, even in case of the inactive sulindac sulfone.