Effects of non-steroidal anti-inflammatory drugs on the structure of lipid bilayers: therapeutical aspects

Abstract

Inflammatory processes are phenomena that initiate at the cellular surface. Therefore, the study of interactions of non-steroidal anti-inflammatory drugs (NSAIDs) with membranes or model membranes is a fundamental step for the enlightenment of their pharmacological activity. Despite their similar chemical structures, NSAIDs have different biological impact, concerning their therapeutic effects. The mechanisms leading to these differences may be related to their different effects on the structural parameters of lipid bilayers. In this study, the molecular interaction between five NSAIDs (piroxicam, meloxicam, tolmetin, indomethacin and nimesulide), widely used in the clinical practice, and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) as a membrane model was investigated by small-angle X-ray scattering (SAXS) and wide-angle X-ray scattering (WAXS). The present study provides evidence that NSAIDs produce distinct biophysical effects depending on the initial organization of the membrane. All the NSAIDs studied reduce or abolish the pre-transition temperature (L_β′ → P_β′) indicating a surface-disordering effect of these drugs. The main lipid phase transition (P_β′ → L_α) is also affected by the NSAIDs studied, with the exception of nimesulide. Meloxicam, tolmetin and indomethacin have the major effects on the L_α phase structure of the DPPC bilayers, which can also be related to their enhanced therapeutic effect as anti-inflammatory drugs. The structural disorder effects found for the NSAIDs studied in the L_β′ phase of the bilayers follow the order: meloxicam > indomethacin > tolmetin > piroxicam and can be also correlated with the anti-oxidant effect of these NSAIDs.