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 (250W/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. LTII 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.

Keywords

Dissolution / Lutein / Metastable polymorph / Nanodispersion / Oral absorption / Photostability

CRediT authorship contribution statement

Kodai Ueno: Writing - original draft, Investigation, Conceptualization. Monami Sugihara: Methodology, Investigation. Tetsuya Matsushita: Methodology, Investigation, Data curation. Kohei Yamada: Writing - review & editing, Investigation. Hideyuki Sato: Methodology, Investigation. Satomi Onoue: Writing - review & editing, Methodology, Funding acquisition, Conceptualization.

Data availability statement

The data supporting the findings of this study are available from the corresponding author upon request.

Ethics approval

All animal testing procedures were conducted in accordance with the guidelines approved by the Institutional Animal Care and Ethical Committee of the University of Shizuoka (Approval No. 236598).

Funding

This work was supported in part by JSPS KAKENHI [Grants-in-Aid for Scientific Research (C) (no. 24K09917: S.O. and no. 20K07180: H.S.]).

Declaration of interests

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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