Liquid-liquid phase separated microdomains of an amphiphilic graft copolymer in a surfactant-rich medium

The liquid-liquid phase separation (LLPS) of amphiphilic thermoresponsive copolymers can lead to the formation of micron-sized domains, known as simple coacervates. Due to their potential to confine active principles, these copolymer-rich droplets have gained interest as encapsulating agents. Understanding and controlling the conditions inducing this LLPS is therefore essential for applicative purposes and requires thorough fundamental studies on self-coacervation. In this work, we investigate the LLPS of a comb-like graft copolymer (PEG-g-PVAc) consisting of a poly(ethylene glycol) backbone (6 kDa) with ∼2-3 grafted poly(vinyl acetate) chains, and a PEG/PVAc weight ratio of 40/60. Specifically, we report the effect of various water-soluble additives on its phase separation behavior. Kosmotropes and non-ionic surfactants were found to decrease the phase separation temperature of the copolymer, while chaotropes and, above all, ionic surfactants increased it. We then focus on the phase behavior of PEG-g-PVAc in the presence of sodium citrate and a C_14-15 E₇ non-ionic surfactant (N45-7), defining the compositional range for the generation of LLPS microdomains at room temperature and monitoring their formation with fluorescence confocal microscopy. Finally, we determine the composition of the microdomains through confocal Raman microscopy, demonstrating the presence of PEG-g-PVAc, N45-7, and water. These results expand our knowledge on polymeric self-coacervation, clarifying the optimal conditions and composition needed to obtain LLPS microdomains with encapsulation potential at room temperature in surfactant-rich formulations.