(416j) Formation of Polymerizable Phospholipid Vesicles Using Microfluidics

Liposomes consist of phospholipid bilayer membranes surrounding an aqueous core. They are promising delivery vehicles for drugs, enzymes and bioreactors for biomedical applications. Since phospholipids are an integral component of biological membranes, phospholipid vesicles provide an ideal platform for a study on the physical properties of biomembranes. However, liposomes get easily ruptured even by small environment stresses: shear flow around membrane, pH change, ionic concentration change, or advent of another membrane. Conventional vesicle formation techniques such as hydration and electroformation rely on the self-assembly of phospholipids in an aqueous environment under a shear or an electric field. Due to the random nature of the bilayer folding, these methods typically lead to the formation of vesicles that are nonuniform in both size and shape. Moreover, encapsulation efficiency of those conventional methods is quite low, generally less than 35%.

We enhance stability and monodispersity of liposomes, and achieve high encapsulation efficiency by generating polymerized phospholipid liposomes with a recent technique, microfluidics. We utilize UV-polymerizable phospholipids that have reactive hydrophobic tails. The microfluidic device can generate monodisperse water-in-oil-in-water (W/O/W) core-shell structure in a single step, allowing precise control of the outer and inner drop sizes as well as the number of droplets encapsulated in each larger drop. The phospholipid solution forms the shell of W/O/W double emulsions that are used as templates for the formation of phospholipid membranes. By removing the solvent in oil phase through evaporation and UV-polymerization, we obtain polymerized vesicles.

In conclusion, our technique can be used to create phospholipid vesicles not only having enhanced stability but also maintaining high size uniformity and encapsulation efficiency.