Fabrication, characterization, and binding mechanism of ferulic acid-loaded nanoparticles using a Zein-chitosan...

To overcome the limitations of poor bioavailability and instability that restrict the use of ferulic acid (FA), this study engineered an advanced delivery system based on Zein-chitosan (Zein-CS) nanoparticles. The formulation was optimized by investigating the effects of chitosan molecular weight (MW) and Zein-CS ratio. Results showed that low-MW chitosan (80 kDa) produced smaller nanoparticles (∼170 nm) with superior size uniformity, while medium-MW chitosan (700 kDa) significantly enhanced encapsulation efficiency to 75.11%. The optimal formulation (Zein-FA-CS2_0.1) exhibited a particle size of 208.8 nm, low polydispersity (PDI = 0.24), and a zeta potential of +23.4 mV, ensuring good colloidal stability. Molecular docking revealed the formation of a stable ternary complex (FA-Zein-CS) with a binding energy of -9.38 kcal/mol, driven by hydrogen bonding and hydrophobic interactions. In vitro release studies confirmed pH-dependent release, with minimal gastric release (≤31.37%) and rapid intestinal release (≥88.72% within 6 h), demonstrating targeted delivery potential. This system provides a promising strategy for delivering FA in functional foods and nutraceuticals, with potential applications to enhance the bioavailability of similar hydrophobic bioactives.