Small-Angle Neutron Scattering Studies of Phospholipid−NSAID Adducts

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Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to have strong interactions with lipid membranes. Using small-angle neutron scattering, the effect of ibuprofen, a prominent NSAID, on the radius of small unilamellar vesicles of 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC) and their bilayer structure was studied systematically as a function of pH (ranging from 2 to 8) and drug-to-lipid mole ratio (from 0/1 to 0.62/1 mol/mol). Ibuprofen with a pK(a) of approximately 4.6 was found to significantly affect the bilayer structure at all pH values, irrespective of the charge state of the drug. At low pH values, the drug reduces the bilayer thickness, induces fluid-like behavior, and changes headgroup hydration. The incorporation of the drug in the lipid bilayer while affecting the local bilayer structure and hydration of the lipid does not affect the overall stability of the vesicle dispersions over the pH range studied.

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