Abstract Increasing drug loading remains a critical challenge in the development and translation of nanomedicine. High drug‐loading nanoparticles have demonstrated unique advantages such as less carrier material used, better‐controlled drug release, and improved efficacy and safety. Herein, we report a simple and efficient salt concentration screening method for making polymer nanoparticles with exceptionally high drug loading (up to 66.5 wt%) based on phase separation‐induced nanoprecipitation. Upon addition of salt, phase separation occurs in a miscible solvent‐water solution delaying the precipitation time of drugs and polymers to different extents, facilitating their co‐precipitation thus the formation of high drug‐loading nanoparticles with high encapsulation efficiency (>90%) and excellent stability (>1 month). This technology is versatile and easy to be adapted to various hydrophobic drugs, different polymers, and solvents. This salt‐induced nanoprecipitation strategy offers a novel approach to fabricating polymer nanoparticles with tunable drug loading, and opens great potentials for future nanomedicines.
