Effect of nonsteroidal anti-inflammatory drugs on the cellular membrane fluidity

In this work, fluorescence measurements were performed using the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH) to evaluate the effects of the interaction of nonsteroidal anti-inflammatory drugs-NSAIDs (meloxicam, lornoxicam, and nimesulide) with several membrane systems (liposomes with and without cholesterol, mouse splenocytes, mouse macrophages cell line-J774, human leukemia monocyte cell line-THP-1, and human granulocytes and mononuclear cells). DPH fluorescence quenching studies revealed that the NSAIDs studied were able to efficiently quench the probe located in membrane hydrocarbon region. Fluorescence anisotropy measurements were also made to investigate the effects on membrane fluidity resulting from the interaction between the drugs and membrane systems. All the anti-inflammatory drugs studied show an increase in the membrane fluidity in a concentration dependent manner. Results obtained provide an insight into NSAIDs capacity to be inserted in lipid bilayers and alter the lipid dynamics. The induced changes in lipid dynamics may modulate the activity of inflammatory enzymes or may be related with deleterious topical action of NSAIDs on gastric phospholipid fluidity. (C) 2007 Wiley-Liss, Inc. and the American Pharmacists Association.