Investigating the Effects of Cholesterol and Lipid Purity on Phospholipid Stability in Liposomal Nanocarriers Using Molecular Dynamics Simulations

Background: Liposomal nanocarriers are widely used in drug delivery due to their biocompatibility, ability to encapsulate therapeutic agents, and potential for functionalization. However, the stability of functionalized liposomes is crucial for their efficacy; detachment of functionalized phospholipids and targeting ligands can reduce their targeting efficiency and therapeutic payload delivery. Objectives: In this study, we employed molecular dynamics simulations to investigate how the material composition of the liposomal membrane affects lipid binding within liposomes, with a focus on cholesterol addition and lipid purity. Methods: The study was conducted using the GROMACS package, utilizing the umbrella sampling method. Results: Potential of mean force (PMF) analysis revealed that both the addition of cholesterol and other phospholipids into the formulation have a negative effect on lipid stabilization in the bilayer membrane. The results also indicated that the presence of cholesterol in the membrane causes a greater decrease in the binding energy of lipids compared to that of other phospholipids. Conclusions: These findings offer insights into designing stable and effective targeted liposomal drug delivery systems.