Alexander V. Dushkin

Water Soluble Complexes of Carotenoids with Arabinogalactan

We present the first example of water soluble complexes of carotenoids. The stability and reactivity of carotenoids in the complexes with natural polysaccharide arabinogalactan were investigated by different physicochemical techniques: optical absorption, HPLC, and pulsed EPR spectroscopy. Compared to pure carotenoids, polysaccharide complexes of carotenoids showed enhanced photostability by a factor of 10 in water solutions. A significant decrease by a factor of 20 in the reactivity toward metal ions (Fe(3+)) and reactive oxygen species in solution was detected. On the other hand, the yield and stability of carotenoid radical cations photoproduced on titanium dioxide (TiO(2)) were greatly increased. EPR measurements demonstrated efficient charge separation on complex-modified TiO(2) nanoparticles (7 nm). Canthaxanthin radical cations are stable for approximately 10 days at room temperature in this system. The results are important for a variety of carotenoid applications, in the design of artificial light-harvesting, photoredox, and catalytic devices.

Enhancement of the Photocatalytic Activity of TiO2 Nanoparticles by Water-Soluble Complexes of Carotenoids †

Photoirradiation of TiO(2) nanoparticles by visible light in the presence of the water-soluble natural polysaccharide arabinogalactan complexes of the hydrocarbon carotenoid β-carotene leads to enhanced yield of the reactive hydroxyl (OH) radicals. The electron paramagnetic resonance (EPR) spin-trapping technique using α-phenyl-N-tert-butyl nitrone (PBN) as the spin-trap has been applied to detect this intermediate by trapping the methyl and methoxy radicals generated upon reaction of the hydroxyl radical with dimethylsulfoxide (DMSO). The free radicals formed in this system proceed via oxygen reduction and not via the reaction of holes on the TiO(2) surface. As compared with pure carotenoids, carotenoid-arabinogalactan complexes exhibit an enhanced quantum yield of free radicals and stability toward photodegradation. The observed enhancement of the photocatalytic efficiency for carotenoid complexes, as measured by the quantum yield of the desired spin adducts, arises specifically from the decrease in the rate constant for the back electron transfer to the carotenoid radical cation. These results are important for a variety of TiO(2) applications, namely, in photodynamic therapy, and in the design of artificial light-harvesting, photoredox, and catalytic devices.

Solubilization and stabilization of macular carotenoids by water soluble oligosaccharides and polysaccharides

Xanthophyll carotenoids zeaxanthin and lutein play a special role in the prevention and treatment of visual diseases. These carotenoids are not produced by the human body and must be consumed in the diet. On the other hand, extremely low water solubility of these carotenoids and their instability restrict their practical application as components of food or medicinal formulations. Preparation of supramolecular complexes of zeaxanthin and lutein with glycyrrhizic acid, its disodium salt and the natural polysaccharide arabinogalactan allows one to minimize the aforementioned disadvantages when carotenoids are used in food processing as well as for production of therapeutic formulations with enhanced solubility and stability. In the present study, the formation of supramolecular complexes was investigated by NMR relaxation, surface plasmon resonance (SPR) and optical absorption techniques. The complexes increase carotenoid solubility more than 1000-fold. The kinetics of carotenoid decay in reactions with ozone molecules, hydroperoxyl radicals and metal ions were measured in water and organic solutions, and significant increases in oxidation stability of lutein and zeaxanthin in arabinogalactan and glycyrrhizin complexes were detected.

Retinal accumulation of zeaxanthin, lutein, and β-carotene in mice deficient in carotenoid cleavage enzymes

Abstract Carotenoid supplementation can prevent and reduce the risk of age‐related macular degeneration (AMD) and other ocular disease, but until now, there has been no validated and well‐characterized mouse model which can be employed to investigate the protective mechanism and relevant metabolism of retinal carotenoids. &bgr;‐Carotene oxygenases 1 and 2 (BCO1 and BCO2) are the only two carotenoid cleavage enzymes found in animals. Mutations of the bco2 gene may cause accumulation of xanthophyll carotenoids in animal tissues, and BCO1 is involved in regulation of the intestinal absorption of carotenoids. To determine whether or not mice deficient in BCO1 and/or BCO2 can serve as a macular pigment mouse model, we investigated the retinal accumulation of carotenoids in these mice when fed with zeaxanthin, lutein, or &bgr;‐carotene using an optimized carotenoid feeding method. HPLC analysis revealed that all three carotenoids were detected in sera, livers, retinal pigment epithelium (RPE)/choroids, and retinas of all of the mice, except that no carotenoid was detectable in the retinas of wild type (WT) mice. Significantly higher amounts of zeaxanthin and lutein accumulated in the retinas of BCO2 knockout (bco2‐/‐) mice and BCO1/BCO2 double knockout (bco1‐/‐/bco2‐/‐) mice relative to BCO1 knockout (bco1‐/‐) mice, while bco1‐/‐ mice preferred to take up &bgr;‐carotene. The levels of zeaxanthin and lutein were higher than &bgr;‐carotene levels in the bco1‐/‐/bco2‐/‐ retina, consistent with preferential uptake of xanthophyll carotenoids by retina. Oxidative metabolites were detected in mice fed with lutein or zeaxanthin but not in mice fed with &bgr;‐carotene. These results indicate that bco2‐/‐ and bco1‐/‐/bco2‐/‐ mice could serve as reasonable non‐primate models for macular pigment function in the vertebrate eye, while bco1‐/‐ mice may be more useful for studies related to &bgr;‐carotene. HighlightsBCO1 and BCO2 regulate carotenoid delivery into the mouse retina.Zeaxanthin and lutein are preferentially accumulated in the mouse retina.Bco2‐/‐ mice can serve as “macular pigment mice” in study of eye disease prevention.

Alteration of Warfarins Pharmacologic Properties in Clathrates with Glycyrrhizic Acid and Arabinogalactan

The article describes the pharmacological examinations of clathrates of warfarin (WF) with glycyrrhizic acid (GA) and arabinogalactan (AG). A direct connection between the clathrate structure and the pharmacons anticoagulative properties was observed. A 20 mg/kg (WF 2 mg/kg) dose of WF: GA 1:10 clathrate causes the increase in prothrombin time (PT) only in 54 hours, after 3 administrations. In contrast, a 20 mg/kg (WF 2 mg/kg) dose of WF: AG 1:10 clathrate leads to an increase in PT in 24 and 48 hours after a single administration, which corresponds to the effect of a comparator agent WF (2 mg/kg).

Effect of complexation with arabinogalactan on pharmacokinetics of "guest" drugs in rats: for example, warfarin.

A pharmacokinetic study of the warfarin (WF) : arabinogalactan (AG) complex with the 1 : 10 mass ratio after its intragastric introduction to Wistar rats at a dose of 5 mg/kg (WF dose in the complex was 0.5 mg/kg) once a day for three days was conducted. It was found that C max, T 1/2, and AUC of WF in the complex form were lower than after the introduction of blank WF at the same dose, but its elimination (Cl, MRT) was much faster. Significant accumulation (C min) and an abrupt increase in plasma concentration after the third introduction were observed for blank WF, whereas the complex showed a much more moderate increase in concentration at this point. However, despite obvious differences in pharmacokinetic parameters, the efficacies of both agents were virtually identical; the complex differed from blank WF by only 15%. This value is rather insignificant and does not impair its anticoagulant activity. Thus, we can conclude that introduction of the WF : AG complex is safe in terms of reduction of the bleeding risk and accumulation.

Physicochemical and Toxic Properties of Novel Genipin Drug Delivery Systems Prepared by Mechanochemistry

BACKGROUND Complexes of Genipin and different water-soluble adjuvant polysaccharides, such as arabinogalactane, hydroxyethyl starch, fibergum, and oligosaccharides β-CD and HP-β-CD, were synthesized as drug delivery system using mechanochemical technology. METHOD We have investigated physicochemical properties, stability, and hepatotoxicity of the synthesized complexes in solid state and aqueous solution. The formation of the complexes was evidenced by different physical and spectroscopy assays, and the stability constants of our synthesized Genipin-based complexes were also calculated. RESULTS The HP-β-CD inclusion complex showed the highest characteristics. We have found that the molecule of Genipin was completely included in the cyclodextrin cavity of the HP-β-CD. This complex of Genipin has shown a 6.14-fold increase of solubility compared with the original Genipin, and more stable in solvent and solid states. CONCLUSION The hepatotoxicity assays showed that our investigated complexes of Genipin are much safer than the original Genipin. These results suggest that new Genipin-based preparations can be synthesized with advantageous of higher stability and safety.