A “spore-like” oral nanodrug delivery platform for precision targeted therapy of inflammatory bowel disease

Colon-targeted oral drug delivery systems are one of the most promising therapeutic strategies for alleviating and curing inflammatory bowel disease(IBD), but they still face challenges in successfully passing through the harsh gastrointestinal environment and intestinal mucus barrier. To overcome the gastrointestinal barriers for oral drug delivery mentioned above, a “spore-like” oral nanodrug delivery platform(Cur/COS/SC NPs) has been developed. Firstly, chitooligosaccharides(COS) are encapsulated on the surface of Curcumin nanoparticles(Cur NPs) to form carrier-free nanoparticles(Cur/COS NPs). Subsequently,inspired by the natural high resistance of spore coat(SC), SC is chosen as the “protective umbrella” to encapsulate Cur/COS NPs for precision targeted therapy of IBD. After oral administration, SC can effectively protect NPs through the rugged gastrointestinal environment and exhibit excellent intestinal mucus penetration characteristics. Moreover, the negatively-charged Cur/COS/SC NPs specifically target positivelycharged inflamed colon via electrostatic interactions. It is demonstrated that Cur/COS/SC NPs can promote the expression of tight junction proteins, inhibit aberrant activation of the Toll-like receptor 4/myeloid differentiation primary response gene 88/nuclear factor-κ B(TLR4/MyD88/NF-κ B) signaling pathway, and downregulate the levels of pro-inflammatory factors, exhibiting excellent anti-inflammatory effects. Notably, it is found that Cur/COS/SC NPs can significantly increase the richness and diversity of gut microbiota, and restore the homeostasis of gut microbiota by inhibiting pathogenic bacteria and promoting probiotics. Hence, Cur/COS/SC NPs provide a safe, efficient, and feasible new strategy for IBD treatment.