Liposomes have long been established as prominent drug delivery systems due to their structural stability and biocompatibility. This has enabled the successful commercialization of several liposome-based therapeutics and has driven the continued development of many others. Despite this progress, the specific contribution of lipid composition to performance has not been clearly established, making the rational design of formulations difficult. Membrane fusion is fundamental to liposomal drug delivery, as the merging of liposomal and cellular membranes allows the efficient release of therapeutic cargo. Understanding how lipid composition and cholesterol content influence this fusion process is therefore essential for guiding the rational optimization of liposome-based drug delivery systems. In this study, we simulated stalk formation in lipid bilayers. Binary mixtures of either DOPC or DPPC with cholesterol were constructed at concentrations ranging from 0% to 40% in 10% increments. Ternary mixtures containing DOPC, DPPC, and cholesterol were then investigated to assess phase separation and membrane fusion. We investigated how PC-type lipid saturation governs the effect of cholesterol in membrane fusion. In complex lipid mixtures exhibiting phase separation, both the characteristics of fusion sites and the dynamic behavior of cholesterol were analyzed.
Song et al. (Sun,) studied this question.