Milk-derived exosome as delivery system for lutein encapsulation in alleviating dry eye disease

Oxidative stress and overactive inflammatory response result in a lack of tear fluid for dry eye disease (DED) pathogenesis. Lutein, a carotenoid for eye health, plays an important role in anti-oxidation and inhibiting the development of inflammation. However, the low bioavailability of lutein is still not well resolved due to its hydrophobicity. In this study, milk-derived exosomes were prepared by ultracentrifugation and filtration method for lutein encapsulation to enhance its bioavailability in alleviating DED. After encapsulation lutein into the exosome membrane through ultrasonic treatment, the lutein loading rate of milk exosomes was 69% with improved water solubility and stability of lutein against degradation at higher temperature and light irradiation. The lutein@exosomes displayed excellent biocompatibility, easy cellular absorption, and facilitated restoration of the mitochondrial membrane potential, which could effectively reduce reactive oxygen species and inflammatory levels in human corneal epithelial cells (HCECs) and macrophages. Furthermore, compared with a commercial product, lutein@exosome exhibited notable efficacy in repairing corneal epithelial damage, restoring tear film homeostasis, restored conjunctival goblet cell count and lacrimal gland size in a chronic dry eye model of C57BL/6 mice. This study offered a novel intervention strategy for DED by an exosome-based delivery system by encapsulating lutein.