Zein–Lecithin Nanoparticle Encapsulation of Eucommia ulmoides Leaf Total Flavonoids: Controlled-Release Kinetics and Physicochemical Stability

Total flavonoids from Eucommia ulmoides leaves (EUTF) show poor aqueous solubility and limited oral bioavailability, restricting their use in functional foods and pharmaceutical formulations. This work developed an oral nano-delivery system by encapsulating EUTF into zein–lecithin hybrid nanoparticles (ZL-EUTF-NPs) fabricated via anti-solvent co-precipitation and optimized by the zein:lecithin mass ratio. The optimized formulation (Z:L = 1:1) produced spherical nanoparticles with a mean hydrodynamic diameter of 155.2 ± 5.2 nm, PDI 0.18 ± 0.02, and zeta potential −35.6 ± 1.5 mV, consistent with a stable colloidal dispersion. Encapsulation efficiency and loading capacity reached 85.3 ± 2.1% and 8.5 ± 0.2%, respectively. FTIR, XRD, and DSC indicated that EUTF was molecularly dispersed in an amorphous state within the protein–lipid matrix through non-covalent interactions. In simulated gastrointestinal conditions, ZL-EUTF-NPs limited EUTF release to 14.2 ± 1.8% during 2 h in simulated gastric fluid (pH 1.2) and enabled sustained intestinal release, reaching 72.8 ± 3.1% after 10 h total incubation. Release in simulated intestinal fluid was best fitted by the Korsmeyer–Peppas model (R² = 0.995; n = 0.67), indicating anomalous (non-Fickian) transport governed by coupled diffusion and matrix erosion. The encapsulated EUTF retained high antioxidant activity (DPPH 82.1 ± 2.8%; ABTS 89.5 ± 3.0% at 50 µg/mL equivalent), while the nanocarrier showed low cytotoxicity (cell viability ≥85% across 10–200 µg/mL equivalent EUTF) and efficient time-dependent uptake in Caco-2 cells. Physicochemical stability testing showed minimal changes under refrigerated storage with 94.5 ± 2.6% flavonoid retention after 90 days at 4°C. Overall, zein–lecithin hybrid nanoparticles provide a practical strategy to enhance EUTF stability and modulate intestinal release for oral applications.