Betulinic acid (BA) has anti-inflammatory, antioxidative stress, and antitumor activities, but BA bioavailability is low due to its poor water solubility and short half-life. This study aimed to construct a BA delivery system to improve its utilization in vitro. Glycosylated zein (G-zein) was prepared using the wet heating method, and BA-loaded zein composite nanoparticles were prepared using the antisolvent method. Compared to zein, G-zein had the advantages of higher solubility and lower surface hydrophobicity. The encapsulation efficiency of G-zein@BA reached over 80% when the BA concentration was 1 mg/mL. Compared to zein@BA nanoparticles, G-zein@BA was characterized by smaller droplets, higher encapsulation efficiency, and a more stable morphology. The sustained release and solubility of G-zein@BA nanoparticles were also superior to those of zein@BA. Compared with free BA, the dispersions of zein@BA and G-zein@BA nanoparticles in water increased 2.27- and 2.91-fold, respectively. In addition, zein@BA and G-zein@BA nanoparticles markedly inhibited the proliferation of HepG2 cells. This study provides new insights into the structural properties and antitumor activity of BA composite nanoparticles to aid in the development of zein particles as functional materials to deliver bioactive compounds.
Keywords: betulinic acid; nanodelivery system; structural properties; zein.