Antisolvent sequence as a tunable switch for zein-naringin-D-tocopheryl polyethylene glycol 1000 succinate (TPGS) nanoparticles: interfacial dynamics and bioactivity enhancement

Naringin (NRG), despite their demonstrated health benefits as natural bioactive compounds, are hampered by intrinsic hydrophobicity, which consequently impedes processability in aqueous systems and severely constrains oral bioavailability. The aim of this study was to form different type nanoparticles by Zein, TPGS and NRG, nanoparticles were obtained by the anti-solvent method, and to analyze the internal interaction forces, stability and antioxidative. The sequence of the antisolvents used becomes the primary factor influencing the properties of the nanoparticles. Nanoparticles were characterized by multimodal analysis, as spectroscopy, molecular docking, SEM, XRD, FTIR, TGA, and ITC. NRG is stabilized within the Zein matrix through hydrogen bonding involving Gln residues and hydroxyl or carbonyl groups, coupled with hydrophobic sequestration of its aglycone moiety in Pro-rich nonpolar cavities. The encapsulation efficiency of NRG increased up to 72.71 % at ( Z -N)-T, which is the highest stability among different types of nanoparticles. The nanoparticles average size below 105 nm, and the zeta potential is 25.48 mV, and also exhibits significant antioxidant activity. This study architected Zein-based nanoparticles to methodically assess the interaction force and stability, pioneering a formulation approach for engineered carriers in food and drug delivery matrices.