The interactions of the non steroidal anti-inflammatory drug celecoxib with pure and cholesterol containing distearoyl phosphatidylcholine multilamellar vesicles were studied using Fourier transform infrared spectroscopy, differential scanning calorimetry and turbidity technique at 440 nm.
The results reveal that celecoxib exerts opposing effects on membrane order in a concentration dependent manner while cholesterol disorders and orders the membrane in the gel and liquid crystalline phase, respectively. Ternary mixtures of DSPC/Cholesterol/celecoxib behave similar to cholesterol with a small effect of celecoxib. While celecoxib decreases fluidity of the DSPC membranes, cholesterol shows an opposite effect, and in ternary mixtures, a dominant effect of cholesterol is observed. Celecoxib induces opposite effects on the hydration status of the carbonyl groups in the binary system whereas / cholesterol induces hydrogen bonding around this group. An evidence of phase separation has also been observed for all three systems (DSPC/celecoxib, DSPC/Chol, and DSPC/Chol/celecoxib). In addition, a possible location of celecoxib in the interfacial region of the membrane has been proposed. Finally, penetration of celecoxib into the hydrophobic core of the ternary system at high cholesterol concentrations and formation of a new phase has also been suggested.
Thus, depending on the concentration used, celecoxib induces significant changes in the biophysical properties of membranes that may aid in understanding its mechanism of action. Furthermore, highly complex interactions take place in ternary membrane systems and further investigations are needed to explore them in detail.
| Identifer | oai:union.ndltd.org:METU/oai:etd.lib.metu.edu.tr:http://etd.lib.metu.edu.tr/upload/3/12610749/index.pdf |
| Date | 01 July 2009 |
| Creators | Sade, Asli |
| Contributors | Banerjee, Sreeparna |
| Publisher | METU |
| Source Sets | Middle East Technical Univ. |
| Language | English |
| Detected Language | English |
| Type | M.S. Thesis |
| Format | text/pdf |
| Rights | Access forbidden for 1 year |
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