Interactions of cholesterol reducing agent simvastatin with charged model membranes were investigated. Effects of cholestrol reducing agent simvastatin on the phase transition behaviour and physical properties of the anionic dipalmitoyl phosphatidylglycerol (DPPG) multilamellar liposome were
studied as a function of temperature and simvastatin concentration. Moreover the effect of acyl chain length on the simvastatin model membrane interactions was monitored using dipalmitoyl phosphatidylglycerol (DPPG)
and dimyristoyl phosphatidylglycerol (DMPG) lipids. All experiments were carried out by two non-invasive techniques namely Fourier Transform Infrared (FTIR) Spectroscopy and Differential Scanning Calorimetry (DSC).
The observations made in the this study clearly showed that simvastatin interacts with the lipids of multilamellar liposomes and induces some variations in the structure of membranes. These effects are seen in the thermotropic phase transition profile of the membranes, on membrane order, acyl chain flexibility, lipid head group structures and membrane fluidity.
The analysis of the C-H stretching region of FTIR spectra showed that, as simvastatin concentration increased, the phase transition curve broadened, pretransition temperature diminished, membrane order and membrane fluidity increased for anionic DPPG membrane. Moreover analysis of the C=O stretching and PO2 - stretching bands showed that simvastatin caused dehydration effect by decreasing of hydrogen bonding capacity in the glycerol backbone and also around the lipid head groups. DSC studies showed that as the simvastatin concentration increased, DSC curves broadened. In addition, simvastatin-induced lateral phase separation
was observed in the DSC thermograms.
In the second part of the study, the effect of acyl chain length on the simvastatin - membrane interactions was investigated for DPPG and DMPG lipid membranes. All parameters used in the FTIR studies are compared for
DMPG and DPPG membranes. Similar results were observed for both membranes, except for the CH2 antisymmetric stretching band frequency at gel phase. Results showed that there are no significant effect of acyl chain length on simvastin - membrane interactions.
| Identifer | oai:union.ndltd.org:METU/oai:etd.lib.metu.edu.tr:http://etd.lib.metu.edu.tr/upload/12611556/index.pdf |
| Date | 01 February 2010 |
| Creators | Sariisik, Ediz |
| Contributors | Severcan, Feride |
| Publisher | METU |
| Source Sets | Middle East Technical Univ. |
| Language | English |
| Detected Language | English |
| Type | M.S. Thesis |
| Format | text/pdf |
| Rights | To liberate the content for public access |
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