Nanodispersion of lutein with use of metastable polymorph for improved dissolution and oral absorption

Abstract

Lutein (LT) is an attractive nutrient for eye health, although it has low water solubility and poor oral absorption. The present study aimed to develop a novel nanodispersion (ND) of LT using a metastable polymorph, offering improved oral absorption of LT. A metastable crystalline form of LT (LT-II) and hydroxypropyl cellulose were subjected to wet-milling followed by freeze-drying to obtain the ND of LT-II (ND/LT-II), and its physicochemical, photochemical, and pharmacokinetic properties of LT samples were evaluated. The mean particle size of LT-II in ND/LT-II was 354 ​nm, and there was no significant change in the crystalline form of LT-II, even after wet milling and freeze-drying. LT generated significant amounts of superoxide anions upon exposure to pseudo-sunlight (250 ​W/m²), indicating high photoreactivity. After irradiation with pseudo-sunlight (250 ​W/m², 30 ​min), the percentages of LT remaining in the LT solution, amorphous LT, and ND/LT-II were 75, 79, and 92%, respectively. LT-II dissolved slightly faster than the stable crystalline form of LT (LT-I) in the dissolution media. ND/LT-II further improved the dissolution property of LT-II, and the dissolved amount of LT was 137- and 7.2-fold higher than that of LT-I and LT-II, respectively, at 2 ​h after dispersion in water. After administration of LT samples (100 ​mg-LT/kg), systemic exposure to LT in the LT-I and LT-II was negligible, whereas a marked improvement in oral absorption was observed in the ND/LT-II groups. Thus, applying ND technology to LT-II may improve oral absorption, and thus the nutrient function of LT.