In Vitro Intestinal Absorption of Carotenoids Delivered as Molecular Inclusion Complexes with β-Cyclodextrin Is Not Inhibited by High-Density Lipoproteins

Abstract

This study analyzed the assimilation efficiency of carotenoids when they are delivered as inclusion complexes with beta-cyclodextrin (CyDIC) in water. The in vitro assimilation model used was the brush border membrane vesicles (BBMV) system in which the BBMVs were incubated with CyDIC. Carotenoid suspensions in Tween were used as a reference. Regardless of the form in which the carotenoids were delivered to the BBMV preparation, a higher assimilation efficiency was observed for carotenes than for the xanthophyll lutein. At the highest donor solution concentration, supplying carotenoids in CyDIC produced a significant increase in carotenoid assimilation compared to the corresponding carotenoid suspensions in Tween. The assimilation process using CyDIC takes place by means of a dissociation process in which the carotenoids are released from the beta-cyclodextrin to later be assimilated. At the highest concentration of CyDIC in the donor solution, the dissociation equilibrium will be shifted toward the free forms of the complex, thus increasing the amount of carotenoids available for assimilation. In another set of experiments, the effect of high-density lipoproteins as activity inhibitors for the receptors involved in carotenoid assimilation was analyzed. In carotenoid suspensions in Tween, with an inhibitor, a significant decrease in the assimilated quantity compared was observed with values reached without the inhibitor. Lutein presented the most significant decrease (70%). The fact that complete inhibition was not reached suggests that both simple and facilitated diffusion contributes to the assimilation process. When the donor solution composed of CyDIC and inhibitor was added, significant increases were observed in beta-carotene and lycopene assimilation for all concentrations and in lutein for the highest concentration. This effect is due to the exchange between lipoprotein lipid components and CyDIC, which promotes the dissociation and liberation processes of the carotenoid, which then becomes available for assimilation.

Carotenoids bioavailability from foods: From plant pigments to efficient biological activities

“…After some incubation time, the solution is filtered or centrifuged to separate the BBMV fraction and the buffer. This technique has been used successfully in mechanistic studies of the assimilation of glucose, biliary salts, lipids, xenobiotics, cholesterol and carotenoids (Alcorn, Simpson, Leahy, & Peters, 1991;Burckhardt, Kramer, Kurz, & Wilson, 1983;Fernández-García, Carvajal-Lérida, Rincón, Ríos, & Pérez-Gálvez, 2010;Hopfer, Nelson, Perrotto, & Isselbacher, 1973;Ikeda, Tanaka, Sugano, Vahouny, & Gallo, 1988;Keelan, Burdick, Wirzba, & Thomson, 1992;Kessler et al, 1978;Ling, Lee, & Hollander, 1989;Moore, Gugger, & Erdman, 1996;Proulx, McNeil, Biglez, & Williamson, 1982). Intestinal tissue from pigs, rabbits, chickens, rats, mice, and humans has been used in these studies, although human BBMV studies are less frequent due to the limited availability of tissue in the conditions necessary for these trials.…”

Water dispersibility of the β‐carotene source and its effect on the physical, thermal, and in vitro release properties of an inclusion complex

“…Notwithstanding morphological agglomeration, the capacity of WDBC-IC to dissolve in water and release the guest molecules may be regarded as an improvement to carotenoid inclusion complexes in general and a comparable alternative to Eudragit ™ -encapsulated vitamin A in terms of burst release in simulated gastric digestion (Anselmo et al, 2019). High concentrations of BC in the digesta also support the conclusion that a surfactant in the inclusion complex may enhance assimilation (Fernández-Garcıá et al, 2010). However, other strategies can be investigated to stabilise β-carotene levels throughout gastrointestinal degradation.…”

“…Later, an electrospraying technique was applied to BC emulsions, but the resulting microencapsulation efficiency was only 34%, slightly lower than conventional spray drying (Donhowe et al, 2014;Gómez-Mascaraque et al, 2017). Suitable surfactants have also been used in preparing BC-based inclusion complexes with amylose to alter the tendency of BC to hinder crystal formation (Kong et al, 2018) and also to facilitate assimilation of BC from β-cyclodextrin complexes to intestinal brush border membranes (Fernández-Garcıá et al, 2010). Liposomes containing vitamin C and BC have been reported to be 98% efficient in encapsulation and cumulatively release 50-80% of the payload after simulated intestinal digestion (Liu et al, 2020).…”

Purification and Formulation of Xanthophyll for Pharmaceutical Use: Current Strategies and Future Trends

“…3), which has also been explored in lutein bioavailability studies [63,67]. Cyclodextrines are cyclic oligomaltosaccharides obtained from starch by means of an enzymatic cycling reaction using cyclodextrin glucosyltransferase [67]. These preparations are made through the addition and mixing of lipophilic guest molecules into a cyclodextrin aqueous solution.…”

“…b-Cyclodextrins (b-CD) are a family of cyclic oligosaccharides composed of a-(1-4) linked 6-,7-or 8-D-glucose units known to accommodate hydrophobic molecules and to form water-soluble inclusion complexes [63]. It has been shown that assimilation of xanthophyll-b-CD aqueous solutions is higher than the obained when the compounds are suspended in Tween [67] or liposome carriers [63]. However, an important disadvantage of this technology is the high volumes needed to develop xanthophyll-based products for parenteral administration, since 5 L of solution are required to deliver 10 mg of astaxanthin [69].…”