Injectable hydrogel loaded with electrostatic self-assembled structure nanoparticles for the treatment of inflammatory bowel disease

The microbiome structure plays a crucial role in the progression of inflammatory bowel disease (IBD). While treating IBD remains a challenge, nano-intervention measures aimed at restoring gut homeostasis may potentially alleviate inflammation in IBD. In this study, layer-by-layer electrostatic self-assembly technology was used to develop hydrogel microspheres containing curcumin (Cur) and zinc (Zn) Prussian blue analog (PBA) as internal cores, with Cur loaded into ZnPBA to increase its bioavailability. Consequently, injectable Cur-ZnPBA@Zein-sodium alginate (CZ@ZS) hydrogel was prepared. The CZ@ZS displayed a macroporous structure, improved bio-adhesion, and prolonged the local drug dwell time following oral administration. Substantial evidence from both in vitro and in vivo studies supported the effectiveness of oral treatment using CZ@ZS in reducing intestinal inflammation and regulating intestinal homeostasis. Moreover, 16S ribosomal RNA sequencing suggested that CZ@ZS increased the diversity of intestinal microflora, such as the augmentation of Bifidobacterium and Lactobacillus probiotics. In conclusion, we developed a biocompatible and regulated immune response and gut microbiota feasible nano-platform for reshaping intestinal homeostasis and a potent therapy for IBD.