Entropy-Driven Liquid-Liquid Phase Separation Transition to Polymeric Micelles.

In recent years, liquid-liquid phase separation (LLPS) has been recognized to act as a precursor to self-assembly in amphiphilic systems. In this study, we propose the use of entropy-driven LLPS to obtain a tunable precursor for polymeric micelle formation. In this new approach, an oligomer is utilized as a nonselective solvent for the block copolymer, allowing for the tuning of entropy and subsequent LLPS. A comprehensive model was developed using mean-field lattice theory to predict the conditions under which LLPS and micellization occur. The degree of polymerization of the solvent was found to have a significant impact on the phase behavior of the system, outweighing enthalpic contributions such as the interaction between the blocks of the copolymer and the solvent. Our model predicts that using a solvent with a degree of polymerization equal to or greater than 5 for a copolymer such as PEG--PLA will result in LLPS prior to complete micellization, regardless of the values of interaction parameters. It also suggests that phase-separated liquid and polymeric micelles can co-exist in such a mixture. We confirmed our model predictions using dynamic light scattering and phase microscopy when PEG200 was used as the solvent. Micellization for PEG--PLA/PEG200/water mixture occurred at 10-12% w/w water content, consistent with the model predictions. Furthermore, the LLPS-to-micelle transition was shown to be reversible by changing the temperature or water content, indicating that the phase-separated liquid may be in thermodynamic equilibrium with polymeric micelles.