Preparation and Characterization of a Lutein Solid Dispersion to Improve Its Solubility and Stability.

Lutein has been used as a dietary supplement for the treatment of eye diseases, especially age-related macular degeneration. For oral formulations, we investigated lutein stability in artificial set-ups mimicking different physiological conditions and found that lutein was degraded over time under acidic conditions. To enhance the stability of lutein upon oral intake, we developed enteric-coated lutein solid dispersions (SD) by applying a polymer, hydroxypropyl methylcellulose acetate succinate (HPMCAS-LF), through a solvent-controlled precipitation method. The SD were characterized in crystallinity, morphology, and drug entrapment. In the dissolution profile of lutein SD, a F80 formulation showed resistance toward the acidic environment under simulated gastric conditions while exhibiting a bursting drug release under simulated intestinal conditions. Our results highlight the potential use of HPMCAS-LF as an effective matrix to enhance lutein bioavailability during oral delivery and to provide novel insights into the eye-care supplement industry, with direct benefits for the health of patients.

A Simple and Efficient Method for the Partial Synthesis of Pure (3R,3'S)-Astaxanthin from (3R,3'R,6'R)-Lutein and Lutein Esters via (3R,3'S)-Zeaxanthin and Theoretical Study of Their Formation Mechanisms.

Carotenoids are natural compounds that have important roles in promoting and maintaining human health. Synthetic astaxanthin is a highly requested product by the aquaculture industry, but natural astaxanthin is not. Various strategies have been developed to synthesize this carotenoid. Nonetheless, these approaches have not only provided limited global yields, but its main commercial source also carries several health risks for humans. In this contribution, the one-pot base-catalyzed reaction of (3R,3'R,6'R)-lutein (1) esters has resulted in a successful isomerization process to easily obtain up to 95% meso-zeaxanthin (2), which in turn is oxidized to (3R,3'S)-astaxanthin (3) with a global yield of 68%. The same oxidation performed with UV irradiation (365 nm) for 5 min provided the highest global yield (76%). These chemical transformations have also been achieved with a significant reduction of the health risks associated with its potential human consumption. Furthermore, this is the first time only one of the configurational isomers has been obtained semisynthetically. The poorly understood formation mechanisms of these two compounds were also investigated using Density-Functional Theory (DFT) calculations. These theoretical studies revealed that the isomerization involves a base-catalyzed deprotonation at C-6', followed by C-4' protonation, while the oxidation occurs via free radical mechanisms.

Optimization of the ultrasound-assisted synthesis of lutein disuccinate using uniform design.

The ultrasound-assisted synthesis of lutein disuccinate from all-trans lutein (AL) and succinic anhydride (SA) was investigated in this study. Triethylamine was used as the catalyst. Based on the single-factor experiments, a 7-level-3-factor uniform design and response surface analysis were further employed to evaluate the effects of the selected variables including molar ratio of SA/AL, reaction time and ultrasonic power on the yield of lutein disuccinate. The results indicated that the data were adequately fitted into a second-order polynomial model; the molar ratio of SA/AL significantly affected the synthesis of lutein disuccinate, whereas reaction time and ultrasonic power did not. Based on ridge max analysis, the optimum condition for lutein disuccinate synthesis was predicted to be the molar ratio of SA/AL 265.3:1, ultrasonic power 300 W and reaction time 131.6 min with the lutein disuccinate yield of 80.53±0.18%, which give a 43.8% increase compared with the traditional method, and also significantly shorten the reaction time.

Total synthesis of (3R,3'R,6'R)-lutein and its stereoisomers.

(3R,3'R,6'R)-lutein (1) is a major dietary carotenoid that is abundant in most fruits and vegetables commonly consumed in the U.S. and that accumulates in the human plasma, major organs, and ocular tissues. Numerous epidemiological and experimental studies have shown that 1 has important biological activities and may play an important role in the prevention of age-related macular degeneration (AMD). While the total synthesis of 1 has been previously reported in a poor overall yield, the total synthesis of the other seven stereoisomers of lutein has not yet been accomplished. We have developed a relatively straightforward methodology for the total synthesis of 1 and three of its stereoisomers, (3R,3'S,6'S)-lutein (2), (3R,3'S,6'R)-lutein or 3'-epilutein (3), and (3R,3'R,6'S)-lutein (4) by C(15) + C(10) + C(15) Wittig coupling reactions. Employing this methodology, the other four stereoisomers of lutein that are enantiomeric to the aforementioned lutein isomers can be similarly prepared. One of the important features of this strategy is its application to the total synthesis of (13)C-labeled luteins and their metabolites with appropriate stereochemistry for metabolic studies in animals and humans. This synthesis also provides access to the C(15)-precursors of optically active carotenoids with a 3-hydroxy-epsilon end group that are otherwise difficult to synthesize.