Effects of cholesterol and temperature on structural properties and dynamic behavior of niosome bilayers with melatonin Inclusion: A Coarse-Grained simulation study

The effects of cholesterol and temperature on the physical properties of niosome bilayers with and with-out melatonin inclusion have been investigated using coarse-grained (CG) simulations. CG models of Span 60 and melatonin have been newly developed and then validated by comparing them with all ato-mistic (AA) simulation results. The CG simulations of niosome bilayers with melatonin inclusion at var-ious cholesterol concentrations (0-70 mol% Chol) were carried out at room temperature, 298 K. A niosome bilayer with melatonin inclusion at a 50 mol% Chol level was simulated for various temperatures (300 K-340 K). The bilayer structure and dynamic properties of these systems were examined as a func-tion of cholesterol concentration and temperature. Melatonin molecules in the niosome bilayer preferen-tially diffuse into the water phase and the niosome bilayer develops a more disordered structure as temperature increases. Melatonin showed two possible orientations. The first is parallel to the bilayer surface and the second is tilted at an angle to the bilayer normal. Maximal efficiency of melatonin entrap-ment of a niosome bilayer is found at a 50 mol% Chol cholesterol concentration when T = 298 K and decreases as temperature increases. A niosome bilayer with an equal ratio of Span 60 to cholesterol shows high physical stability and greater efficiency of melatonin entrapment over a wide temperature range (298 K-310 K). This excellent property can be suggested for designing and developing niosomes to improve drug delivery into cells for therapeutic purposes. (C) 2022 Elsevier B.V. All rights reserved.