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

doi:10.1007/s11705-021-2118-y

Front. Chem. Sci. Eng.

2022, Vol. 16

Issue (6) : 1017-1022 https://doi.org/10.1007/s11705-021-2118-y

COMMUNICATION

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

Xu-Chun Song¹, Zi-Han Zhou^1,², Ya-Lan Yu¹(

), Nan-Nan Deng²(

)

¹. College of Chemistry and Chemical Engineering, Southwest Petroleum University, Chengdu 610500, China
². School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China

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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.

Keywords microfluidics liposomes ternary droplets phase separation

Corresponding Author(s): Ya-Lan Yu,Nan-Nan Deng

Online First Date: 17 December 2021 Issue Date: 28 June 2022

Cite this article:

Xu-Chun Song,Zi-Han Zhou,Ya-Lan Yu, et al. Microfluidic production of liposomes through liquid--liquid phase separation in ternary droplets[J]. Front. Chem. Sci. Eng., 2022, 16(6): 1017-1022.

URL:

https://academic.hep.com.cn/fcse/EN/10.1007/s11705-021-2118-y
https://academic.hep.com.cn/fcse/EN/Y2022/V16/I6/1017

Fig.1 Schematics of the preparation of liposomes from single O/W emulsion droplets: (a) single-stage microfluidic device, (b) phase separation in an oil-in-water droplet to form a water-in-oil-in-water double emulsion droplet, and (c) the dewetting process of W/O/W droplets to form liposomes.

Fig.2 Liquid–liquid phase separation process of the ternary composition of butyl acetate-water-ethanol.

Fig.3 (a) The ternary phase diagram of the butyl acetate-water-ethanol system, (b) uniform ternary mixture corresponding to point A in (a), and (c) non-uniform ternary mixture corresponding to point B in (a).

Fig.4 Optical images showing phase separation process in ternary droplets: (a) microfluidic generation of O/W droplets, (b) phase separation in O/W droplets, and (c) as-prepared W/O/W double emulsion droplets. Scale bars: (a) 100 μm, (b) 20 μm, and (c) 50 μm.

Fig.5 Optical images of liposome formation process. Scale bar: 20 μm.

Fig.6 Optical images showing phase separation process in O/W droplet stabilized by Pluronic F-127. Scale bar: 20 μm.

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