Microfluidics Fabrication of Monodisperse Biocompatible Phospholipid Vesicles for Encapsulation and Delivery of Hydrophilic Drug or Active Compound

Abstract

We encapsulate the hydrophilic anti-cancer drug doxurubicin hydrochloride (DOX) with about 94% drug encapsulation efficiency, either alone or with nanomagnetite, in monodisperse biocompatible phospholipid vesicles. Glass capillary microfluidics is used to generate monodisperse water in oil in water (w/o/w) double-emulsion templates with a core–shell structure by using a mixture of liquid unsaturated phospholipids and powdered saturated phospholipid. This combination would overcome the low transition temperature of unsaturated powdered phospholipid and the solubility limitation of saturated phospholipid, as well as improving the fabrication of stable monodisperse phospholipid vesicles. The double-emulsion droplet is controlled from 50 to 200 μm according to different flow rates, and the final phospholipid vesicles are retained after a solvent removal step by dewetting. DOX-loaded phospholipid vesicles show sustained release compared with free DOX water solution. The in vitro cell viability of 100 μg/mL phospholipid vesicles on HeLa or MCF-7 cells after 24 h incubation at 310 K is above 90%, confirming the excellent biocompatibility of the phospholipid vesicles. These biocompatible phospholipid vesicles are promising oral drug delivery vehicles for biomedical applications and magnetic resonance imaging contrast agents for biomedical diagnosis