Thermodynamics Of Lipid Membrane Partitioning Of Selective Serotonin Reuptake Inhibitors

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.