Synthesis of Phospholipids

About

Summary Stanford chemists have developed a scalable synthetic process to create a new class of viscous, stable phospholipid bilayer vesicles with tunable properties. Specifically, this is the first synthetic method to create pure ladderanes (lipids produced in nature by anammox bacteria) and can be adapted to generate either naturally-occurring molecules, their intermediates, or novel lipids with unique, tunable properties. The resulting ladderanes self-assemble into vesicles, which is particularly useful for capturing cargo such as drugs or imaging agents. Because of their viscosity, low compressibility, and slow diffusion, ladderane-based drug delivery vehicles are likely to be relatively impermeable and more stable than traditional liposomes. They could be used to target molecules to a therapeutic site, to perform basic research of biological systems, or to create nanofabricated coatings. Stage of Research The inventors have used the synthetic process to create prototypical self-assembled, fluid, viscous, bilayer ladderane vesicles and characterized the vesicle properties. They found that ladderane vesicles have low compressibility and exceptionally slow diffusion compared with common straight-chain lipids. Applications Drug delivery - create lipid vesicles to deliver molecules for therapeutics and imaging Biological research - create vesicles for selective delivery of molecules to cells for basic scientific studies Nanofabrication and coating such as surface passivation Advantages Stable - ladderane vesicles demonstrate reduced compressibility Dense and highly viscous - likely to minimize leakage of vesicle contents and increase circulation half-life Tunable - enables synthesis of novel molecules to optimize properties for intended use (for example, vesicles could be designed to melt a specified temperature to customize time and location of drug delivery) Self-assembly to encapsulate drugs or other cargo Scalable synthesis to enable large scale production