This 2-year project aims to understand the correlations among the phospholipid composition, the total freeenergy and the fusion efficiency of liposomes. Liposome is an artificial self-assembled structure ofphospholipids, and has been widely exploited in the pharmaceutical industry as drug delivery systems orused as the cellular model systems, due to its structural resemblance to a living cell. Whether as a drugdelivery system or as a cellular model, membrane fusions between liposomes or between liposomes andother bilayer entities (e.g., supported bilayers) have drawn considerable attention. Membrane fusion is aprocess in which two individual membranes as well as their encapsulated spaces and contents merge andbecome a single entity. Many vital biological activities, such as the vesicular transport mechanism that cellsemploy to shuttle proteins among organelles, the release of the neurotransmitter by neurons and the viralinvasion into cells, all involve membrane fusions. Membrane fusion is also relevant to biomedicalapplications: A compound or substance is of great pharmaceutical value if it can inhibit the membranefusion between a host cell and a virus; and delivery of a liposome encapsulated drug with an intracellulartargets is also correlated with membrane fusion. During the fusion process, membranes undergo severallamellar-nonlamellar or nonlamellar-nonlamellar structural transformations, and therefore have to overcomemany energy barriers. The magnitudes of the energy barriers are highly related to the phospholipidcomposition of the membranes. That is to say, the phospholipid composition of a liposome determines theenergy barriers of the fusion and consequently the fusion efficiency. Nevertheless, most of the recent studieson these topics are dedicated to investigating the energy barriers involved in the formation of a fusionintermediary, the stalk structure; seldom of them discuss the overall fusion efficiency. Accordingly, thisstudy is planned to explore the correlations among the phospholipid composition, total free energy andoverall fusion efficiency, such that the generally applicable thermodynamic principles underlying thecomposition dependence of fusion efficacy can be discovered. This contribution is of great value both toimproving our understanding towards the fusion mechanisms and to devising the design principles fordeveloping drug delivery systems. The other focus of this study is to develop and synthesize thephospholipid-mimetic surfactants to functionally replace the expensive phospholipids. The strategy is toapply the knowledge learned from the first part of the study to determining the molecular properties desiredfor the surfactants that can form noisomes (a liposome-like structure) with high fusion efficiency. Synthesisof this types of surfactants will be devised with a mass production purpose in mind.
|Effective start/end date||1/08/16 → 31/07/17|
In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This project contributes towards the following SDG(s):