Ursodeoxycholic acid grafted chitosan oligosaccharide self-assembled micelles with enhanced oral absorption and antidiabetic effect of oleanolic acid

Oleanolic acid (OA) is a food-derived bioactive component with antidiabetic activity, but its water solubility and oral bioavailability are notably restricted. In this study, to overcome these limitations, ursodeoxycholic acidmodified chitosan oligosaccharide (UCOS) was synthesized to encapsulate OA in self-assembled nanomicelles (UCOS-OA). The encapsulation efficiency and drug loading of UCOS-OA were 86 % and 11 %, respectively. UCOS-OA exhibited enhanced gastrointestinal stability and prolonged intestinal retention time when compared with free OA, resulting in a 10.6-fold increase in oral bioavailability. The enhanced antidiabetic activity of UCOSOA was confirmed in the type 2 diabetes mellitus mice model, as it significantly improved glycolipid metabolism disorders and mitigated liver injury. Furthermore, UCOS-OA ameliorated the dysbiosis of gut microbiota and fecal metabolites. In conclusion, UCOS serves as an effective polymeric carrier for encapsulating OA, thereby improving its bioavailability and antidiabetic activity. This work provides valuable insights for the advancement of oral delivery systems for bioactive compounds.