Exploring the potential of chitosan-α-lipoic acid copolymer/sodium alginate-coated hollow zein nanoparticles for oral astaxanthin delivery: Structural characterization, safety assessment and anti-ulcerative colitis effect.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by damage to the colonic mucosal barrier, persistent inflammation, and gut microbiota dysbiosis. Nevertheless, a major limitation of current therapies is their nonspecific distribution and inadequate drug accumulation at the inflamed colonic site. Herein, this study developed a pH and redox-sensitive nanoparticle delivery system to enhance the treatment of UC. The nanoparticles were built from alternating layers of hollow zein, chitosan-α-lipoic acid copolymer and sodium alginate to form a polyelectrolyte multilayer core-shell nanoparticle structure. Astaxanthin (AXT), a natural anti-inflammatory compound, was selected as the encapsulated substance in this study. Transmission electron microscopy analysis demonstrated that AXT was successfully encapsulated, and the nanoparticles exhibited a hollow spherical structure with an average diameter of approximately 295.4 nm. The interaction forces between AXT and nanoparticles were mainly hydrogen bonding and hydrophobic interactions. Besides, the nanoparticles exhibited excellent in vivo safety and significantly enhanced the antioxidant activity of AXT. In vivo experiments indicated that AXT-loaded nanoparticles significantly alleviated weight loss, disease activity index, colonic mucosal integrity, and inflammation in mice induced by dextran sulfate sodium salt. More importantly, AXT-loaded nanoparticles had a remarkably higher effect on UC attenuation than free AXT. AXT-loaded nanoparticles could increase the abundance and diversity of the gut microbiota to maintain the intervention efficacy of UC. These results confirm that this nano-delivery system exhibit great potential for UC treatment.