Resveratrol loaded zein nanoparticles for inhibiting proliferation of osteosarcoma cells: Synthesis, characterization, release profile, and cytotoxicity

• Resveratrol loaded zein nanoparticles were synthesized to target bone cells. • Zein was chemically cross-linked with alendronate using EDC/NHS chemistry. • Resveratrol-loaded zein nanoparticles showed suppression of osteosarcoma cell growth. • A higher inhibition rate was found for targeted, alendronate-zein nanoparticles. • The potency of entrapped resveratrol is improved three orders of magnitude. Resveratrol loaded zein nanoparticles (Res ZNPs) were synthesized to deliver resveratrol to bone cells for inhibiting the proliferation of osteosarcoma cells. Zein chemically cross-linked with alendronate as a bone-targeting agent using EDC and NHS chemistry was also synthesized and the cross-linking was confirmed using Fourier-Transform Infrared and Nuclear Magnetic Resonance spectroscopy. Subsequently, Res ZNPs with and without alendronate were synthesized and characterized. The particles measured 273 to 294 nm with a narrow polydispersity index, and a zeta potential of -29 to -33 mV, respectively as evaluated by dynamic light scattering. The particles showed spherical morphology imaged by transmission electron microscopy and the entrapment efficiency and loading capacity were 63.0 % and 13.6 % for Res ZNPs and 69.1 % and 21.0 % for Res ZNPs with alendronate, respectively. Furthermore, the entrapped resveratrol of both systems was released in a three-phase manner under physiological condition (phosphate-buffered saline, PBS) at 37 °C over 24 h. Both systems exhibited suppression of osteosarcoma MG-63 cell proliferation and the inhibition rate was found slightly higher for targeted, Res ZNPs with alendronate. This research suggested that Res ZNPs conjugated with alendronate could be a candidate for effective bone-targeting delivery systems to inhibit the proliferation of osteosarcoma cells.