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To encapsulate piperine (Pip), as a poor water-soluble bioactive compound, zein-sodium caseinate-xanthan gum (Z-SG-XG) nanocomplex was prepared as a colloidal delivery system. The effect of different parameters involved in complexation process, including concentration of proteins, polysaccharide, and Pip on the encapsulation efficiency of Pip, particle size and stability of the nanocomplexes was investigated. Powders obtained by freeze-drying of the colloidal solution had relatively uniform particles compared to those obtained from conventional drying system and showed well redispersibility in water. At the optimal condition, a stable and homogeneous nanocomplex with a mean particle size of 145.9 ± 2.7 nm, PDI of 0.27 ± 0.01, and ζ-potential of −39.7 ± 1.3 mV was obtained. The antioxidant activity of Pip was significantly improved by encapsulation into the Z-SC-XG nanocomplex. Also, the in vitro release of Pip from the synthesized nanocomplexes in phosphate-buffer saline (PBS) solution and simulated gastrointestinal fluids (SGIF) was investigated and the release kinetic was studied as well. The Pip/Z-SG-XG nanocomplex showed a slower release in SGIF compared to the free Pip and nanoparticles without XG and SC, while its antioxidant activity was remarkable. Results suggested a possible utilization of Z-SC-XG nanocomplex for improving the water solubility, bioavailability and storage stability of Pip.

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