Engineering Milk-Derived Exosome for Enhancing Cellular Astaxanthin Delivery

Astaxanthin (AST), a fat-soluble carotenoid, shows excellent antioxidant and anti-inflammatory activities, but its low biocompatibility and stability limit its application in the food industry. In this work, we constructed the targeted hyaluronic acid (HA)-modified milk exosome-based astaxanthin delivery system to improve the biocompatibility stability and targeted transport properties of astaxanthin. Nuclear magnetic resonance (NMR) and Fourier transform infrared spectroscopy (FTIR) showed that HA was efficiently modified onto the surface of the milk exosome by an amide condensation reaction. The fluorescence images showed that the targeted delivery system accumulated in RAW264.7 macrophages, and the targeting effect on inflammatory cells was significantly enhanced. Compared with free astaxanthin, the delivery system could enhance the cellular uptake of astaxanthin and alleviate the overproduction of reactive oxygen species significantly and the depolarization of mitochondrial membrane potential in a lipopolysaccharide-induced cellular model. The delivery system also notably inhibited the expression of IL-1β, IL-6, and other inflammatory factors. Therefore, the targeted hyaluronic acid-modified milk exosome-based astaxanthin delivery system prevents the activation of macrophages and the production of inflammatory mediators and has the potential to apply to the prevention of chronic inflammatory diseases.