An efficient co-delivery system based on multilayer structural nanoparticles for programmed sequential release of resveratrol and vitamin D3 to combat dextran sodium sulfate-induced colitis in mice

Multilayer structural nanoparticles (MSNPs) fabricated by layer-by-layer self-assembly were used for the co-encapsulation of resveratrol (Res) and vitamin D3 (Vd). Res and Vd co-encapsulated MSNPs (Res-Vd-MSNPs) were evaluated by appearance, morphology, particle size, ζ potential and encapsulation efficiency (EE). The results showed that Res-Vd-MSNPs were spherical in shape with a particle size of 625.4 nm and a surface charge of +26.1 mV. The EE of Res and Vd was as high as 93.6 % and 90.8 %, respectively. Res-Vd-MSNPs exhibited better stability and lower degradation rate in simulated gastric fluid, allowing the programmed sequential release of Vd and Res in simulated intestinal fluid and simulated colonic fluid, which was also confirmed by in vivo fluorescence imaging of mice. In addition, Res-Vd-MSNPs effectively alleviated the clinical symptoms of dextran sulfate sodium salt (DSS)-induced colitis in mice, including weight loss, diarrhea and fecal bleeding, and it especially exerted a preventive effect on DSS-induced colon tissue damage and colon shortening. Furthermore, Res-Vd-MSNPs suppressed the expression of anti-inflammatory cytokines such as TNF-α, IL-1β and IL-6 and ameliorated DSS-induced oxidative damage, decreased colonic myeloperoxidase (MPO) and nitric oxide (NO) activities and elevated glutathione (GSH) level in DSS-treated mice. This study illustrated that MSNPs were potential carriers for developing the co-delivery system for the synergistic prevention and treatment of ulcerative colitis.