Abstract: [Objective] To study the preparation, characterization, and antioxidant activity of resveratrol-zein nanoparticle （Res-ZeinNPs） systems based on the anti-solvent method. [Methods] Res-ZeinNPs were prepared using the anti-solvent method, and the formulation was optimized via orthogonal design. The Res-ZeinNPs were systematically characterized, and their release profiles under different pH conditions and antioxidant activity were dynamically evaluated. [Results] Four factors-zein mass, ethanol volume, Res mass, and ultrapure water volume-showed highly significant effects on encapsulation efficiency （P<0.01）. The optimal conditions for preparing Res-ZeinNPs were: zein mass 75 mg, 70% ethanol 75 mL, Res mass 2.5 mg, and ultrapure water 200 mL. The resulting particles achieved an encapsulation efficiency of 98.13% and a drug loading capacity of 20.9%. Transmission electron microscopy observations revealed that Res-ZeinNPs were spherical, with a modal particle size of approximately 150 nm and a negative charge. In vitro release studies indicated that Res-ZeinNPs exhibited pH-responsive release characteristics; at pH 1.2 and 7.4, the 24 h cumulative release rates were 38.80% and 45.24%, respectively, both highly significantly lower （P<0.01） than raw Res powder. DPPH radical scavenging assays demonstrated that Res-ZeinNPs had a significantly higher （P<0.05） DPPH scavenging rate than raw Res powder. [Conclusion] Res-ZeinNPs exhibit high encapsulation efficiency, favorable sustained-release properties, and enhanced antioxidant activity, which can improve the stability and bioavailability of resveratrol.

Key words: resveratrol, zein, nanoparticles, anti-solvent method, orthogonal design, encapsulation efficiency