Microfluidic production of liposomes through liquid--liquid phase separation in ternary droplets

Abstract

Liposomes, the self-assembled phospholipid vesicles, have been extensively used in various fields such as artificial cells, drug delivery systems, biosensors and cosmetics. However, current microfluidic routes to liposomes mostly rely on water-in-oil-in-water double emulsion droplets as templates, and require complex fabrication of microfluidic devices, and tedious manipulation of multiphase fluids. Here we present a simple microfluidic approach to preparing monodisperse liposomes from oil-in-water droplets. For demonstration, we used butyl acetate-water-ethanol ternary mixtures as inner phase and an aqueous solution of surfactants as outer phase to make oil-in-water droplets, which can evolve into water-in-oil-in-water double emulsion droplets by liquid–liquid phase separation of ternary mixtures. Subsequently, the resultant water-in-oil-in-water droplets underwent a dewetting transition to form separated monodisperse liposomes and residual oil droplets, with the assistance of surfactants. The method is simple, does not require complex microfluidic devices and tedious manipulation, and provides a new platform for controllable preparation of liposomes.

Key words： microfluidics; liposomes; ternary droplets; phase separation

Acknowledgments

This work was financially supported by the National Natural Science Foundation of China (Grant No. 22008153) and Start-up Funding from Shanghai Jiao Tong University.

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