Zein-lecithin core-shell nanoparticles for andrographolide delivery to synergistically enhance anti-inflammatory and antioxidant activities in RAW264.7 cells.

Andrographolide (AG) exhibits significant anti-inflammatory properties. However, the extremely low water solubility, poor bioavailability, and interference by gastrointestinal flora limit its clinical application. In this study, zein-lecithin-AG nanoparticles (ZLA NPs) were successfully synthesized using an anti-solvent precipitation method. The optimized ZLA NPs exhibited a well-defined spherical core-shell structures with favorable physicochemical characteristics, including an average particle size of approximately 202 nm, narrow size distribution (PDI < 0.2), a zeta potential of -41.7 mV, high encapsulation efficiency (82.58 %), and excellent storage and salt-ion stability. FTIR and XRD analyses confirmed that electrostatic interactions, hydrophobic forces, and hydrogen bonding among zein, lecithin, and AG contributed to nanoparticle formation. ZLA NPs markedly improved the in vitro release behavior, biosafety, and cellular uptake of AG in RAW264.7 macrophages. Moreover, ZLA NPs synergistically enhanced the anti-inflammatory effects of AG, as evidenced by significant modulation of inflammatory cytokines (TNF-α, IL-6, and IL-10; P < 0.05) and promoting macrophage polarization. In addition, both free radical scavenging assays and intracellular ROS measurements demonstrated superior antioxidant capacity of ZLA NPs compared with free AG. Collectively, these findings demonstrate that ZLA NPs not only enhance the dissolution and delivery efficiency of AG but also synergistically enhance its anti-inflammatory and antioxidant activities. Therefore, ZLA NPs represent a highly promising nanoscale platform for anti-inflammatory drug delivery.