pH-driven formation of nano SPI-based ternary complex towards co-delivery of curcumin and Zn at different ratios with synergistic neuroprotective activity

Currently, curcumin and Zn have been widely recognized for their potential in promoting neurological health. The co-delivery of the two has attracted increasing attention for their synergistic neuroprotectivity. While greener way in fabrication calls for attention. In this work, nanoscaled Cur-SPI-Zn ternary complexes were successfully prepared by pH-driven method using soy protein isolate (SPI) as a carrier, displaying homogeneous spherical-like aggregated particles at various curcumin: Zn ratios (1:0–1:1). Remarkably, the curcumin encapsulation efficiency and Zn binding rates in the complexes could reach as high as 81% and 50%, respectively. The mechanism involved in complex formation was further explored by SEM, XRD, XPS, FL and FTIR analysis. Curcumin and Zn formed a ternary complex with SPI acting as a bridge in the aqueous phase, supported by hydrophobic interactions, electrostatic interactions, and coordination interactions. In addition, co-delivery of Zn improved the bioaccessibility of curcumin in vitro and the efficacy was depending on the Zn content in the complex. Neuroprotective potential was further examined in PC12 cells treated with oxidopamine hydrochloride (6-OHDA), where the ternary complex exhibited synergistic alleviation of cellular injury in a Zn content-dependent manner compared to curcumin or Zn alone, by scavenging reactive oxygen species, inhibiting lipid peroxidation and alleviating mitochondrial damage. These findings well revealed the great neuroprotective potential of ternary complexes in a synergistic manner.