Cholesterol concentration effect on bilayer membranes and its role in designing efficient liposomal drug delivery systems.

Abstract

Liposomal drug delivery systems provide a versatile therapeutic platform for treating numerous diseases. Cholesterol, as a common component of many liposomal drug delivery systems, plays a crucial role in enhancing mechanical strength and decreasing the permeability of biomembranes. However, the ratio required for a proper formulation is poorly recognized. In this study, all-atom molecular dynamics simulations are performed to characterize the effect of cholesterol concentration in bilayers. To prepare liposomes, we simulate DSPC (1,2-distearoyl-sn-glycero-3-phosphocholine) phospholipid combined with different molar ratios of cholesterol (100, 80-20, 70-30, and 60-40%) in both planar and spherical bilayers. Furthermore, it has been quantified how a range of bilayer properties, including area per lipid, leaflet interdigitation, membrane thickness, and lipid Scd order parameters, are altered by variation in concentrations of lipid and cholesterol. Therefore, the most suitable amount of cholesterol and lipid to prepare stable and controlled drug release vehicles is obtained by screening the lipid and cholesterol ratio arrangement. Compared to membranes without cholesterol, the influence of cholesterol on lipid bilayers is revealed. These results provide a better understanding of the fundamental characteristics of the structure and dynamics of cholesterol-containing membranes. By revealing molecular details of interactions between cholesterol and phospholipids, these simulations accurately represent atomic-level characteristics of the planar and spherical bilayers. The simulations presented here shed light on the workings and limitations of liposomal drug delivery technology and establish a computational framework for the rational design of liposomes in drug delivery systems.