Issue 29, 2023

The interplay of membrane fluidity, acyl chain order and area per lipid on the partitioning of two antidepressants paroxetine and sertraline

Abstract

Selective serotonin reuptake inhibitors (SSRIs) are among the popular drugs for treating depression and mental disorders. Membrane fluidity has previously been considered as the main factor in modulating the membrane partitioning of SSRIs, while other biophysical properties, such as the acyl chain order and area per lipid, were often neglected. Varying the lipid membrane composition and temperature can significantly modify the physical phase and, in turn, affect its fluidity, acyl chain order and area per lipid. Here, we investigate the role of membrane fluidity, acyl chain order and area per lipid in the partitioning of two SSRIs, paroxetine (PAX) and sertraline (SER). The model membranes were either POPC : SM (1 : 1 mol ratio) or POPC : SM : Chol (1 : 1 : 1 mol ratio) and studied in the temperature range of 25–45 °C. The order parameters and area per lipid in the two lipid mixtures were calculated using molecular dynamics simulations. The membrane partitioning of PAX and SER was determined via second derivative spectrophotometry. In a lower temperature range (25–32 °C), membrane fluidity favors the SSRI partitioning into Lo/Ld POPC:SM:Chol. In a higher temperature range (37–45 °C), the interplay between membrane fluidity, acyl chain order and area per lipid favors drug partitioning into Ld POPC:SM. The findings offer indication for the inconsistent distribution of SSRIs in tissues as well as the possible interaction of SSRIs with lipid domains and membrane-bound proteins.

Graphical abstract: The interplay of membrane fluidity, acyl chain order and area per lipid on the partitioning of two antidepressants paroxetine and sertraline

Supplementary files

Article information

Article type
Paper
Submitted
06 Apr 2023
Accepted
03 Jul 2023
First published
03 Jul 2023

Soft Matter, 2023,19, 5527-5537

The interplay of membrane fluidity, acyl chain order and area per lipid on the partitioning of two antidepressants paroxetine and sertraline

D. T. N. Ngo, T. H. Ho, L. K. Huynh and T. T. Nguyen, Soft Matter, 2023, 19, 5527 DOI: 10.1039/D3SM00462G

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