Development of self-assembled (+)-Nootkatone delivery system using Gliadin-Carboxymethyl chitosan composite nanoparticles: Fabrication, characterization, and pharmaceutical application.

Despite its diverse therapeutic potential, (+)-nootkatone (NK) exhibits restricted oral bioavailability due to low water solubility and instability. This study addresses these challenges by developing Gliadin/Carboxymethyl chitosan (CMCS) composite nanoparticles as an NK delivery system. The preparation of NK-loaded Gliadin/CMCS composite nanoparticles employed an anti-solvent precipitation approach. Self-assembly facilitated NK encapsulation within Gliadin's hydrophobic regions, after which CMCS adhered to the nanoparticle surface through Gliadin-mediated electrostatic interactions, ultimately forming a multilayered NK encapsulation framework. The nanoparticles, created with a 4:1 gliadin to CMCS mass ratio, exhibited an average size of 224.4 nm, a zeta potential of -31.0 mV, and an NK encapsulation efficiency of 81.9 %. Microscopic analyses confirmed that Gliadin/CMCS-NK nanoparticles possess a spherical morphology. The encapsulation significantly enhanced the environmental stability, thermal robustness, and controlled release capabilities of NK. Additionally, gliadin and CMCS markedly improve free radical scavenging and anticancer activities, with improved controlled release observed during in vitro digestion. These findings suggest that Gliadin/CMCS nanoparticles effectively enhance the oral bioavailability and stability of bioactive compounds like NK, making them suitable for food applications and the development of functional foods and supplements.