Composite nanoparticles composed of zein and chondroitin sulfate (CS) were self-assembled by the method of antisolvent precipitation to deliver curcumin (ZCCNPs). The structure of ZCCNPs changed from spheres to microaggregates with the increase of CS, involving hydrogen bonding and electrostatic and hydrophobic effects. The resistance of ZCCNPs to degeneration was improved by CS. The encapsulation efficiency of curcumin was enhanced by CS and showed the maximum (91.97%) when the mass ratio of zein-to-CS was 1 : 1 (ZCCNPs_1:1). The crystallinity of curcumin changed to amorphous in ZCCNPs_1:1. ZCCNPs_1:1 exhibited great stability at pH 3.0–8.0, and it showed excellent thermostability at 35, 55, and 80 °C respectively for 120 min when the pH was 4.0 or 6.0. Meanwhile, it showed great storage stability at 4 and 22 °C respectively for 30 days. The retention rate of curcumin in ZCCNPs_1:1 was higher than 65% within 8 days. The presence of CS improved the antiproliferative activity of curcumin-loaded zein nanoparticles (Cur-ZNPs) to HCT116 cells. ZCCNPs_1:1 exhibited higher bioaccessibility (42.36%) than Cur-ZNPs. In addition, ZCCNPs_1:1 exhibited excellent biocompatibility evaluated using in vitro cytotoxicity assay on NCM460 cells. The studies indicate that the delivery system fabricated in our work would be efficient for improving the application of hydrophobic nutrients in functional foods.

Alcohol-free curcumin-loaded zein/sophorolipid nanoparticles were fabricated by one-step self-assembly to overcome extreme hydrophobicity, inferior stability, and poor bioaccessibility of curcumin.