Liquid antisolvent precipitation: an effective method for ocular targeting of lutein esters.

BACKGROUND: Lutein ester (LE) is an important carotenoid fatty acid ester. It is a form in which lutein is present in nature and is produced by free non-esterification and fatty acid esterification. LE is one of the safe sources of lutein. Increasing lutein intake can prevent and treat age-related macular degeneration. In addition, it can effectively inhibit gastric cancer, breast cancer, and esophageal cancer. However, the poor aqueous solubility of LE has impeded its clinical applications. OBJECTIVE: The objective of this study was to prepare lutein ester nanoparticles (LE-NPs) by liquid antisolvent precipitation techniques to improve the bioavailability of LE in vivo and improve eye delivery efficiency. MATERIALS AND METHODS: The physical characterization of LE-NPs was performed, and their in vitro dissolution rate, in vitro antioxidant capacity, in vivo bioavailability, tissue distribution, and ocular pharmacokinetics were studied and evaluated. RESULTS: The LE freeze-dried powder obtained under the optimal conditions possessed a particle size of ~164.1±4.3 nm. The physical characterization analysis indicated the amorphous form of LE-NPs. In addition, the solubility and dissolution rate of LE-NPs in artificial gastric juice were 12.75 and 9.65 times that of the raw LE, respectively. The bioavailability of LE-NPs increased by 1.41 times compared with that of the raw LE. The antioxidant capacity of LE-NPs was also superior to the raw LE. The concentration of lutein in the main organs of rats treated with the LE-NPs was higher than that in rats treated with the raw LE. The bioavailability of LE-NPs in rat eyeballs was found to be 2.34 times that of the original drug. CONCLUSION: LE-NPs have potential application as a new oral pharmaceutical formulation and could be a promising eye-targeted drug delivery system.