Glycogen-based pH and redox sensitive nanoparticles with ginsenoside Rh₂ for effective treatment of ulcerative...

The purpose of this study is to construct a pH and redox sensitive nanoparticle to effectively deliver ginsenoside Rh₂ for the treatment of ulcerative colitis (UC). Herein, glycogen was modified by urocanic acid and α-lipoic acid (α-LA) to obtain an amphiphilic polymer (LA-UaGly). Such polymer LA-UaGly could self-assemble to form nanoparticles (Blank NPs) in water with excellent stability, which could also successfully encapsulated ginsenoside Rh₂ to form Rh₂ nanoparticles (Rh₂ NPs) with encapsulation efficiency of 74.36 ± 0.34%. DLS analysis indicated Rh₂ NPs were spherical with a particle size of 128.9 ± 0.3 nm. As expected, Rh₂ NPs exhibited typical pH and redox dual response release behaviour as well as the excellent in vivo safety. In vitro tests showed that Rh₂ NPs could effectively internalize and release Rh₂ into RAW264.7 cells, and protect cells from apoptosis (p < 0.05). More interestingly, Rh₂ NPs exhibited strong anti-inflammatory activity via significantly inhibiting the overproduction of nitric oxide (NO) and inflammatory cytokines (TNF-α, IL-1β and IL-6) (p < 0.05). In vivo experiments suggested that Rh₂ NPs significantly ameliorated the weight loss, colon length, disease activity index (DAI) score, and myeloperoxidase (MPO) activity in mice caused by dextran sulfate sodium salt (DSS) (p < 0.05). Simultaneously, pathological analysis proved that Rh₂ NPs could significantly reduce histological damage and inflammatory infiltration in mice. Rh₂ NPs could also effectively regulate the intestinal flora of mice by improving the species uniformity and abundance of the intestinal flora of mice and restoring the species diversity of the intestinal flora. In addition, both in vivo and in vitro experiments proved that Rh₂ NPs had stronger anti-inflammatory activity than Rh₂. This study provides a promising strategy for the effective treatment of UC.