Crystalline Poly(L‐Lactic Acid) Nanoparticles via Nonsolvent‐Induced Cascade Phase Separation

ABSTRACT We investigate the formation of poly(L‐lactic acid) (PLLA) nanoparticles using a green solvent, propylene carbonate (PC), via a combination of nonsolvent‐induced phase separation (NIPS) and temperature‐induced phase separation (TIPS). Water (W) is used as the nonsolvent to induce liquid/liquid phase separation (LLPS) of the PLLA/PC solution at high temperature. Reducing the solution temperature can induce a second LLPS, followed by PLLA crystallization. Three types of polymer nanoparticles (PNPs), including PLLA single crystals, spherical Ouzo crystalsomes, and sheaf‐like crystals named cascade PNPs (CasPNPs), have been observed. The crystalline structure and thermal behavior of the PNPs have been investigated using Wide‐Angle X‐ray diffraction, Fourier Transform Infrared Spectroscopy, and Differential Scanning Calorimetry. A PNP morphology map of the PLLA/PC/W ternary system has been established. The complex PNP morphology is attributed to the two levels of cascade LLPS coupled with confined PLLA crystallization. Our results demonstrate that LLPS directs the formation of both PLLA spherical particles and curved single crystals, with improved crystallization kinetics.