There is increasing evidence that common drugs, such as
aspirin and
ibuprofen, interact with
lipid membranes.
Ibuprofen is one of the most common
over the counter drugs in the world, and is used for relief of
pain and
fever. It interacts with the
cyclooxygenase pathway leading to inhibition of
prostaglandin synthesis. From X-ray diffraction of highly oriented model membranes containing between 0 and 20 mol%
ibuprofen, 20 mol%
cholesterol, and
dimyristoylphosphatidylcholine (
DMPC), we present evidence for a non-specific interaction between
ibuprofen and
cholesterol in
lipid bilayers. At a low
ibuprofen concentrations of 2 mol%, three different populations of
ibuprofen molecules were found: two in the
lipid head group region and one in the hydrophobic membrane core. At higher
ibuprofen concentrations of 10 and 20 mol%, the lamellar bilayer structure is disrupted and a lamellar to cubic phase transition was observed. In the presence of 20 mol%
cholesterol,
ibuprofen (at 5 mol%) was found to be expelled from the membrane core and reside solely in the head group region of the bilayers. 20 mol%
cholesterol was found to stabilize lamellar membrane structure and the formation of a cubic phase
at 10 and 20 mol%
ibuprofen was suppressed. The results demonstrate that
ibuprofen interacts with
lipid membranes and that the interaction is strongly dependent on the presence of
cholesterol.