Self-assembled nanoparticles from sugarcane polyphenol compounds for enhanced antioxidant activity and in vivo absorption.

Natural polyphenol mixtures possess synergistic bioactivities but suffer from poor bioavailability and biological barrier penetration. Although nanoformulation offers a promising strategy, conventional carrier-dependent systems face limitations in biocompatibility, drug loading homogeneity, and scalability. To overcome these challenges, we developed carrier-free sugarcane polyphenol nanoparticles (SP-NPs) via hydrothermal-induced oxidative polymerization and supramolecular self-assembly of natural sugarcane polyphenol (SP) extract. SP-NPs was primarily composed of rutin, 2,4,6-trihydroxybenzoic acid, and gallic acid. It formed spherical nanoparticles via π-π stacking, hydrogen bonding, and hydrophobic interactions, with a particle size of 182.08 ± 35.40 nm and a zeta potential of -25.03 mV. It demonstrated markedly enhanced antioxidant activity via hydrogen atom transfer and favorable biosafety. Pharmacokinetic studies revealed substantially improved oral absorption of SP-NPs, with a shorter time to peak concentration (0.5 h), 71.07 % higher maximum plasma concentration, and 34.16 % greater systemic exposure compared to SP. SP-NPs also showed a 96.78 % plasma protein binding rate and specific enrichment in the brain, liver, and pancreas. This study provides a green and efficient carrier-free nanoassembly strategy for polyphenol mixtures, providing an experimental foundation for enhanced oral delivery and targeted therapy of oxidative stress-related diseases.