Yukiko Uekaji

Micelle formation of coenzyme Q10 with dipotassium glycyrrhizate using inclusion complex of coenzyme Q10 with γ-cyclodextrin.

Micelles can be formed from coenzyme Q10 (CoQ10) and dipotassium glycyrrhizate (GZK2) by using an inclusion complex of CoQ10 with γ-cyclodextrin (γ-CD). The mechanism of micelle formation was kinetically investigated. Adding GZK2 to a supersaturated solution of the CoQ10/γ-CD inclusion complex led to a linear increase in the solubility of CoQ10 due to the formation of micelles of CoQ10 when the molar ratio of GZK2/γ-CD increased to ∼1.6, after which the concentration remained constant. The equilibrium constant K for micelle formation was 0.68 (-) and the ratio of GZK2 to CoQ10 was 1. These results suggest that the formation of CoQ10 micelles with GZK2 might proceed via the displacement of CoQ10 by GZK2 in the γ-CD cavity followed by the formation of CoQ10 micelles.

Coenzyme Q10 - gamma cyclodextrin complex is a powerful nutraceutical for anti-aging and health improvements

Coenzyme Q10 (CoQ10) is a fat-soluble, vitamin-like, benzoquinone compound that functions primarily as an antioxidant, as a membrane stabilizer and as a cofactor in the oxidative phosphorylation production of adenosine triphosphate (ATP) . The solubility of CoQ10 in water is extremely low, resulting in a low bioavailability by oral administration. Therefore, we attempted to improve the low dissolution and bioavailability of CoQ10 by means of complexation with various cyclodextrins. We found that the bioavailability of CoQ10 could be significantly enhanced by complexation with cyclodextrins, especially by the use of γCD. The CoQ10 gCD complex reveals excellent pharmacokinetic properties not only significantly higher area under the CoQ10 concentration curve in blood plasma from time 0-48 hr (AUC) and higher maximum plasma concentration (Cmax), but also the mean plasma levels even after 24 and 48 hours tended to be significantly higher after CoQ10 gCD complex administration to healthy adult volunteers when compared with CoQ10 formulated in microcrystalline cellulose and administrated in the same way as the complex . We found that this long-lasting high CoQ10 concentration in plasma provides various health benefits. The proven benefits are: 1) Curative effects on damaged human skins by aging, UV and other pollutants in the air, 2) Anti-oxidant activity (study on the reduction of 8-hydroxy-2-deoxy guanosine (8-OHdG) in urine), 3) Muscle augmentation and protection activity (study on the reduction of myogenic enzymes, Creatinine phosphokinase (CPK) and lactate dehydrogenase (LDH)). Furthermore, some combinations of CoQ10-γCD complex with other functional ingredients in formulation are suggested with following claims for anti-aging and health improvements: 1) Analgesic action by reproducing cartilage by the combination with collagen peptide, 2) Anti-fatigue by the enhanced oxidative phosphorylation production of adenosine triphosphate (ATP) by the combination with α-lipoic acid-γCD complex, 3) Antidote against metabolic syndrome by the combination with αCD as a special dietary fiber that shows good effects on controlling body weight, on the ratio of LDLand HDL cholesterol , on the concentration of triglycerides and on the blood sugar level in plasma.

Bioavailability of an R-α-Lipoic Acid/γ-Cyclodextrin Complex in Healthy Volunteers

R-α-lipoic acid (R-LA) is a cofactor of mitochondrial enzymes and a very strong antioxidant. R-LA is available as a functional food ingredient but is unstable against heat or acid. Stabilized R-LA was prepared through complexation with γ-cyclodextrin (CD), yielding R-LA/CD. R-LA/CD was orally administered to six healthy volunteers and showed higher plasma levels with an area under the plasma concentration-time curve that was 2.5 times higher than that after oral administration of non-complexed R-LA, although the time to reach the maximum plasma concentration and half-life did not differ. Furthermore, the plasma glucose level after a single oral administration of R-LA/CD or R-LA was not affected and no side effects were observed. These results indicate that R-LA/CD could be easily absorbed in the intestine. In conclusion, γ-CD complexation is a promising technology for delivering functional but unstable ingredients like R-LA.

Bioavailability enhancement of hydrophobic nutraceuticals using γ-cyclodextrin

Natural hydrophobic bioactives that possess human health benefits often have undesirable characteristics that limit their use as nutraceuticals. These bioactives are usually unstable in the presence of oxygen, ultraviolet radiation, and heat. Furthermore, their solubility in water is low owing to their hydrophobicity or instability, which leads to low bioavailability. Much attention has recently been directed to the use of cyclodextrins (CDs) as complementary and alternative medicinal foods with human health benefits for the current aging population. Systematic studies have been performed to investigate improvements in the stability, water solubility, and bioavailability of hydrophobic nutraceuticals through complexation with CDs. Although hydrophobic nutraceuticals, such as coenzyme Q10, curcumin, and tocotrienol, form insoluble complexes with γ-CD, the bioavailability of the complex dramatically improves compared with conventional technologies. Recently, it was found that hydrophobic bioactives generally aggregate in water, but the dissociated bioactives from γ-CD are captured by bile acid to form micelles without aggregation; thus, both solubility and bioavailability are enhanced. Complexation with γ-CD is a promising method to achieve enhanced bioavailability of hydrophobic nutraceuticals. In this article, an outline of the innovative nanotechnologies that implement γ-CD to enhance stability and control of the solubility and bioavailability of key ingredients for health and beauty in the field of medicinal foods is presented.