Thermally-induced whey protein isolate-daidzein co-assemblies: Protein-based nanocomplexes as an inhibitor of precipitation/crystallization for hydrophobic drug

One challenge for daidzein delivery is how to efficiently suppress its precipitation/crystallization in a lipid-based system. In this work, whey protein isolate (WPI) with different thermal treatment was employed as a hydrophobic drug crystallization depressor and its interaction mechanism with daidzein was studied. The results indicated WPI aggregated to form nanoparticles (below 300 nm) in the presence of daidzein. Thermal denaturing (85 °C, 20 min) improved the binding affinity for daidzein with Ka = 1.165 × 104 M−1, about 1.5-fold higher than that of the native protein (Ka = 7.285 × 103 M−1). Hydrophobic interaction was the major driving forces based on thermodynamic calculation. The as-obtained protein-based nanocomplexes efficiently inhibited daidzein crystallization, enhancing its solubility at least 2-fold with promoted stability (stable at 4 °C for at least 2 months). These findings provide new ideas for the application of WPI, showing great potential to be directly used in lipid nanocarrier system as crystallization depressor.