Chitosan oligosaccharides-modified nanoliposome improve the stability, antioxidant, and anti-inflammatory activity of cordycepin

• Development of COS-modified nanoliposome for enhanced cordycepin stability. • COS-modified nanoliposome showed better encapsulation performance for cordycepin. • Targeted absorption of cordycepin with reduced release in gastric fluid. • Improved antioxidant properties of cordycepin in COS-modified nano-liposome. • Enhanced anti-inflammatory efficacy of cordycepin in COS-Cor-Lpo. Cordycepin is an important bioactive component in Cordyceps militaris and offers significant physiological benefits for human health. However, its application is limited due to its poor stability and rapid degradation, which lead to a loss of bioactivity. This study aimed to enhance the stability and anti-inflammatory efficacy of cordycepin by developing a novel Chitosan oligosaccharides (COS) modified cordycepin nano-liposome (COS-Cor-Lpo) using a reverse evaporation and surface modification technique. The COS-Cor-Lpo exhibited a spherical microstructure with a diameter of <300 nm, demonstrating a narrower size distribution, better polydispersity, and higher encapsulation efficiency of cordycepin compared to unmodified liposomes. The formation of COS-Cor-Lpo was primarily driven by electrostatic adsorption and hydrogen bonding interactions. Moreover, COS-Cor-Lpo significantly improved cordycepin's stability under various storage conditions, reduced its release in gastric fluid, and enhanced its release in intestinal fluid, promoting targeted absorption. Compared to cordycepin and its unmodified liposomes, COS-Cor-Lpo showed lower cytotoxicity, higher antioxidant activity, and a stronger protective effect against inflammatory damage in IEC-6 cells by reducing the levels of nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6), while inhibiting the mRNA expression of TNF-α, IL-6, P38, and JNK. These results suggest that COS-Cor-Lpo represents a promising nano-embedding system for cordycepin delivery.