Design of protein-based carriers for curcumin with tailored particle properties: Stability and mechanistic insights

Curcumin's (Cur, C) utility is restricted by poor solubility, stability, and bioavailability. This study optimized zein (Z)-centered core-shell nanoparticles using soluble pea protein (Psup) or whey protein isolate (WPI, W) as the shell. pH-shifting enhanced Cur loading to 316.3 μg/mg (PsupZC) and 266.1 μg/mg (WZC), surpassing simple complexation, which left exposed Cur crystals after lyophilization. Core-shell ratios controls particle sizes (50-102 nm for PsupZC; 30-80 nm for WZC) with polydispersity index<0.2. PsupZC demonstrated enhanced photostability, thermal stability, and retained over 65 % Cur under gastric conditions, outperforming WZC. Mechanistically, the proteins' hydrophobicity facilitated stronger interactions with Cur, while pH-shifting enhanced cur-protein binding through hydrogen bonding. Cur incorporation stabilized protein secondary structures, increasing α-helix and β-sheet content. Furthermore, these nanoparticles were also able to stabilize Pickering emulsions. Overall, pH-shifting, core-shell compositions and optimized ratios enabled tailored PsupZ nanoparticles, providing more scalable and multifunctional protein-based carriers for hydrophobic bioactives.