A ternary zein/soy lecithin/dextran sulfate nanocarrier for improved resveratrol bioactivity delivery: Enhanced solubility, stability, and bioactivity.

Resveratrol (RES), a natural compound widely used as a food additive and preservative, exhibits anti-inflammatory and antioxidant activities. However, its poor solubility and stability severely limit its translational potential for clinical applications. To address these challenges, we developed a core-shell nanoparticle drug delivery system (DDS) composed of zein, soy lecithin, and dextran sulfate, fabricated via a built-in ultrasonic dialysis process (BUDP). The optimized RES/ZLDS NPs exhibited uniform spherical morphology, small particle size (252.00 ± 14.64 nm), high negative zeta potential (-80.10 ± 0.66 mV), and satisfactory encapsulation efficiency (88.54 ± 1.98%) and loading capacity (7.86 ± 0.03%). Compared with free RES, RES/ZLDS NPs significantly enhanced the dissolution rate (3.90-fold), white light stability (1.41-fold), UV light stability (2.22-fold), ABTS+ scavenging activity (3.42-fold), and in vitro bioaccessibility (2.33-fold). Mechanistic studies revealed that the nanoparticles were internalized primarily via caveolae/lipid raft-mediated endocytosis, and in vivo tissue distribution demonstrated the highest RES accumulation in the lung, with approximately 2.5-fold and 2-fold increases in the heart and lung, respectively, over free RES. In an LPS-induced acute lung injury (ALI) mouse model, RES/ZLDS NPs dramatically alleviated pulmonary pathological damage and reduced IL-6 and TNF-α levels in bronchoalveolar lavage fluid by 2.79-fold and 2.45-fold, respectively, compared with free RES. Importantly, acute toxicity evaluation confirmed that RES/ZLDS NPs did not induce detectable organ damage or alter serum biochemical parameters, indicating a favorable safety profile. Collectively, our findings demonstrate that this nanoparticle system not only optimizes the physicochemical and biological performance of RES but also serves as a versatile and safe delivery platform for other food-derived bioactive compounds.