| dc.description.abstract | In this study, thermodynamics of the partitioning process of two representatives of
selective serotonin reuptake inhibitors (SSRIs), namely paroxetine and sertraline,
into zwitterionic large unilamellar vesicles (LUVs) made of 1-palmitoyl-2-oleoyl-snglycerol-3-phosphocholine (POPC), sphingomyelin (SM), both in the presence or
absence of cholesterol (Chol) were investigated using second derivative
spectrophotometry. By determining the partition coefficient (Kp) values of
paroxetine and sertraline into POPC-SM and POPC-SM-Chol LUVs at varied
temperatures (32°C, 37°C and 45°C), Van’t Hoff analysis of the temperature
dependence of Kp then revealed positive values for both ΔH and ΔS, suggesting an
entropy- driven mechanism for two common SSRIs drugs partitioning into POPC-SM
or POPC-SM-Chol LUVs. Additionally, it was found that both paroxetine and
sertraline partitioned to a greater extent into the LUVs with increasing temperature.
The presence of cholesterol in the LUVs lowered the membrane partitioning of
SSRIs. The obtained findings could provide further insights into the antidepressant
drug’s mechanism as well as in drug development and design. | en_US |
