Engineered an ultrasmall curcumin oral nanoformulation restores intestinal integrity and gut microbiota dysbiosis

Antibiotic therapy for bacterial infections often disrupts gut microbiota (GM) and intestinal integrity, inducing chronic inflammation and inflammatory bowel diseases. An effective therapeutic intervention is urgently needed to alleviate the aforementioned adverse effects of antibiotics. Curcumin (CUR) reveals great potential to restore intestinal integrity and GM dysbiosis due to its strong antiinflammatory and prebiotic effects. However, the weak solubility and stability of CUR result in limited bioavailability and a short half-life, which restricts its clinical uses. An ultra-small CUR oral nanoformulation was created using a carboxylated galactomannan (cGM), facilitated by hydrogen bonding between the phenolic hydroxyl groups of CUR and the carboxyl groups present on cGM. The developed nanoformulation increased CUR stability both <i>in vitro</i> and in vivo, extended its retention period in the gastrointestinal tract, and enhanced its permeability across the mucus layer and intestinal epithelium to improve oral bioavailability of CUR. The nanoformulation attained notable therapeutic efficacy in restoring intestinal epithelial barrier dysfunction and GM dysbiosis, as validated in an antibiotic-induced in vivo model. This research highlights the benefits of cGM in creating a very stable and ultrasmall nanoformulation for CUR, offering a promising oral nanoplatform for the delivery of CUR.