Preparation of cellulose-based nanoparticles via electrostatic self-assembly for the pH-responsive delivery of astaxanthin

Oral administration of astaxanthin (AST), a potent antioxidant, is limited owing to its low solubility, physicochemical stability, and bioavailability. This study developed pH-responsive nanocarriers by the electrostatic self-assembly of 2,2,6,6-tetramethylpiperidine-1-oxyradical (TEMPO)-oxidized cellulose nanofibers (TCNFs) and chitosan (CS) to enhance the intestinal delivery of AST. The TCNF/CS@AST nanoparticles were optimized through single-factor experiments and Box–Behnken design, subsequently overcoming the hydrophobicity of AST and demonstrating improved stability against environmental stressors and controlled release in the intestinal environment. Transmission electron microscopy confirmed the near-spherical shape of these nanoparticles, with an average hydrodynamic diameter of 64 nm. TCNF/CS@AST enhanced the antioxidant effectiveness of AST after digestion and in lipopolysaccharide-stimulated RAW 264.7 cells while demonstrating good cellular compatibility. These nanoparticles present a promising strategy for the oral delivery of hydrophobic bioactive compounds orally, with potential applications in precision nutrition.