Optimizing Lutein Formulations for Targeted Ocular Drug Delivery: In Vitro and In Vivo Insights.

Lutein is a plant pigment beneficial for eye health and for preventing retinal-related diseases. However, lutein is unstable, with low oral bioavailability. In this study, lutein fromMomordica cochinchinensiswas loaded into cubosome lipid nanocarriers, both neutral (lutein-MO) and cationic (lutein-MO-DOTAP); the release, stability, and retinal penetration of the drug were improved. The formulation was biocompatible on retinal cells, showed sustained release in cell culture media and simulated lachrymal fluid, and was stable at 25 °C for 90 days. The cationic formulation, lutein-MO-DOTAP, showed greater uptake into retina cells than unencapsulated lutein and conferred greater protection of retina cells against H2O2 stress. Lutein-MO-DOTAPs enhanced Nrf2 and HO-1 antioxidant genes and downregulated IL-6 inflammatory and VEGF-A angiogenesis genes. Lutein-MO-DOTAPs were detected in mice retina in vivo 1 day post intravitreal injection and 7 days after topical application as eyedrops. We have successfully created a more stable lutein formulation that could penetrate the back of the eye in the retina and be developed as a therapy to enhance eye health or mitigate eye diseases.