Dihydrocaffeic acid grafted chitosan self-assembled nanomicelles with enhanced intestinal transport and antioxidant properties of chicoric acid

•DA-g-CS was synthesized by free radical-mediated method, which is green, safe and economical.•The bioavailability of DA-g-CS/CA is 2.24 times that of CA, which greatly facilitates the oral absorption of CA.•DA-g-CS/CA enters cells via the macropinocytosis pathway and shows higher cellular uptake.•DA-g-CS/CA shows higher antioxidant activity. Chicoric acid (CA) plays a crucial role as a functional factor within the realm of foods, showcasing a wide array of bioactivities. Nevertheless, its oral bioavailability is significantly limited. To optimize the intestinal absorption and bolster the antioxidant capacity of CA, a water-soluble dihydrocaffeic acid grafted chitosan copolymer (DA-g-CS) was synthesized using a conventional free radicals system, and subsequently utilized for the encapsulation of CA within self-assembled nanomicelles (DA-g-CS/CA). The average particle size of DA-g-CS/CA was 203.3 nm, while the critical micelle concentration was 3.98 × 10-4 mg/mL. Intestinal transport studies revealed that DA-g-CS/CA penetrated cells via the macropinocytosis pathway, exhibiting the cellular uptake rate 1.64 times higher than that of CA. This substantial enhancement in the intestinal transport of CA underscores the significant improvements achieved through DA-g-CS/CA delivery. The pharmacokinetic results demonstrated that DA-g-CS/CA exhibited a remarkable bioavailability 2.24 times that of CA. Furthermore, the antioxidant assessment demonstrated that DA-g-CS/CA exhibited exceptional antioxidant properties in comparison to CA. It demonstrated enhanced protective and mitigating effects in the H2O2-induced oxidative damage model, while also displaying a stronger emphasis on protective effects rather than attenuating effects. These findings aim to establish a solid theoretical foundation for the advancement of CA in terms of its oral absorption and the development of functional food products.