A new method to prepare microparticles based on an Aqueous Two-Phase system (ATPS), without organic solvents

Hypothesis: Aqueous Two-Phase Systems (ATPS) are aqueous droplets dispersed in an aqueous phase. This specific behavior arises from interactions between at least two water-soluble entities, such as thermodynamically incompatible polymers. A simple, fast, and "green" process to produce ATPS with an aqueous core would be of high interest to the pharmaceutical field for drug delivery. However, to date, rapid destabilization of ATPS represents the main hurdle for their use. Herein we present a novel process to achieve a stabilized microparticle-ATPS, without the use of organic solvents. Experiments: ATPS composed of dextran and polyethylene oxide were prepared. A Pickering-like emulsion technique was used to stabilize the ATPS by adsorbing semi-solid particles (chitosan-grafted lipid nanocapsules) at the interface between the two aqueous phases. Finally, microparticles were formed by a polyelectrolyte complexation and gelation. The structure and stability of ATPS were characterized using microscopy and Turbiscan analysis.Findings: Adding chitosan-grafted lipid nanocapsules induced ATPS stabilization. Adding a polyelectrolyte such as sodium alginate allowed the formation of microparticles with a gelled shell that strengthened the formulation against shear stress and improved long-term stability, thus demonstrating that is possible to use ATPS to form delivery systems to encapsulate hydrophilic molecules.(c) 2021 Elsevier Inc. All rights reserved.