Preparation of Lipid Vesicles Having Suitable Size for Drug Delivery with High Entrapment of Hydrophilic Molecules Using Multiple Emulsions

A method for preparing lipid vesicles having suitable size for drug delivery (in a few hundred nanometer size) with high entrapment efficiency of hydrophilic molecules was developed. The lipid vesicles containing hydrophilic molecules in their internal compartments were formed from water-in-oil-in-water (W1/O/W2) multiple emulsions after the removal of organic solvent by evaporation under ambient condition. The primary W1/O emulsions were formed via homogenization by sonication of mixture of oil phase containing bilayer forming lipids, and the water phase containing hydrophilic molecules to be entrapped. The W1/O/W2 multiple emulsions were formed through microchannel (MC) emulsification by introducing the dispersed phase, i.e., (W1/O) emulsion, into the MC device in the presence of polymeric surfactants in the external water phase. The average size of the lipid vesicles formed, measured using dynamic light scattering and observed by transmittance electron microscopy, was 182 nm, and comparable with the size of the initial water droplet of the primary W1/O emulsion (192 nm), indicating that the vesicle size reflects the water droplet size of the primary W1/O emulsion. High entrapment yields for hydrophilic molecules, namely 89.3 ± 4.2% for calcein and 41.1 ± 3.3% for 5-fluorouracil, were achieved.