Interactions of cholesterol reducing agent simvastatin with phospholipid model membranes

Koçak, Mustafa
Interactions of simvastatin with zwitterionic dipalmitoyl phosphotidylcholine (DPPC) multilamellar liposomes were investigated as a function of temperature and simvastatin concentration. And acyl chain length effect on the simvastatin-model membrane interactions was monitored with DPPC and dimyristoyl phosphotidylcholine (DMPC) lipids. All studies were carried out by two non-invasive techniques, namely Fourier transform infrared (FTIR) spectroscopy, and differential scanning calorimetry (DSC). The results showed that as simvastatin concentration increased, the main phase transition temperature decreased, the main phase transition curve broadened, and the characteristic pretransition was disappeared for both DMPC and DPPC model membranes. All concentrations of simvastatin disordered and decreased the fluidity of phospholipid membranes. Analysis of C=O stretching band showed that simvastatin either strengthen the existing hydrogen bonds of the glycerol skeleton closer to the head groups or caused the formation of new hydrogen bonds. A dehydration effect caused by simvastatin around the PO2- functional groups in the polar part of the lipids was monitored. This dehydration effect in the gel phase was more profound than in the liquid crystalline phase for 1, 6, and 12 mol% of simvastatin concentrations. DSC peaks broadened and shifted to lower temperature values by increasing the simvastatin concentration. For both lipids, simvastatin-induced lateral phase separation was observed in the DSC thermograms. Any change caused by the acyl chain length difference of DMPC and DPPC lipids was not observed on the simvastatin-membrane interactions. Also, for both of the lipids similar trends were observed in the FTIR and DSC results. More profound effects of simvastatin on the less stable DMPC membranes were observed.


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Citation Formats
M. Koçak, “Interactions of cholesterol reducing agent simvastatin with phospholipid model membranes,” M.S. - Master of Science, Middle East Technical University, 2007.