Ibuprofen in a Lipid Bilayer: Nanoscale Spatial Arrangement

Abstract

Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic effects. Understanding the molecular mechanisms of drug interaction with cell membranes is important to improving drug delivery, uptake by cells, possible side effects, etc. Double electron-electron resonance spectroscopy (DEER, also known as PELDOR) provides information on the nanoscale spatial arrangement of spin-labeled molecules. Here, DEER was applied to study (mono-)spin-labeled ibuprofen (ibuprofen-SL) in a bilayer of palmitoyl-oleoyl-sn-glycerophosphocholine (POPC). The results obtained show that the ibuprofen-SL molecules are located within a plane in each bilayer leaflet. At their low molar concentration in the bilayer χ, the found surface concentration of ibuprofen-SL is two times higher than χ, which can be explained by alternative assembling in the two leaflets of the bilayer. When χ > 2 mol%, these assemblies merge. The findings shed new light on the nanoscale spatial arrangement of ibuprofen in biological membranes.

Keywords

• non-steroidal anti-inflammatory drug
• NSAID
• lipid bilayer
• clustering
• spin-label EPR
• DEER