Enhancing solubility and bioavailability of coenzyme Q10: formulation of solid dispersions using Soluplus® as a carrier.

Improving the aqueous solubility of poorly soluble compounds have been a major issue in the pharmaceutical industry. In the present study, binary amorphous solid dispersions (SDs) of Coenzyme Q10 (CoQ10), a biopharmaceutics classification system (BCS) II compound and Soluplus® were prepared to enhance the solubility and pharmacokinetic properties compared to crystalline CoQ10. SDs were prepared with different ratios of CoQ10 and Soluplus® (1:3, 1:5, and 1:7) using spray drying technology, and the physicochemical properties of the SDs were evaluated. X-ray powder diffraction, differential scanning calorimetry, and scanning electron microscopy suggested the conversion of the crystalline form of CoQ10 to a binary amorphous system in the SDs. Fourier transform infrared spectroscopy revealed no potential interactions between CoQ10 and Soluplus®. The solubility of the optimal SD formulation (SD 1:7) was approximately 9000-fold higher than that of crystalline CoQ10, and the increment was Soluplus® concentration dependent. As a result, optimized SD 1:7 also showed significantly enhanced dissolution rate where maximum drug release was observed within 30 min in two different dissolution media. Moreover, in contrast to crystalline CoQ10, CoQ10 SDs showed improved pharmacokinetic parameters. Thus, the SD 1:7 formulation is expected to improve biopharmaceutical properties and therapeutic efficacy of CoQ10.

Improved water dispersion and bioavailability of coenzyme Q10 by bacterial cellulose nanofibers.

The purpose of this study was to investigate the potential of bacterial cellulose nanofiber suspension (BCNs) as stabilizer in anti-solvent precipitation and its effect on improving bioavailability of coenzyme Q10. Bacterial cellulose (BC) was hydrolyzed by sulfuric acid followed by the oxidation with hydrogen peroxide to prepare BCNs. The suspension of BCNs-loaded CoQ10 (CoQ10-BCNs) were prepared by antisolvent precipitation. The zeta potential of CoQ10-BCNs was about -36.01 mV. The properties of CoQ10, BCNs and CoQ10-BCNs were studied by scanning electron microscopy, transmission electron microscope, Fourier-transform infrared spectroscopy, X-ray diffraction, differential scanning calorimetry and thermo gravimetric analysis. The crystallinity of CoQ10 decreased in CoQ10-BCNs compared with the raw CoQ10, and CoQ10-BCNs have good physicochemical stability. In oral bioavailability studies, the area under curve (AUC) of CoQ10-BCNs was about 3.62 times higher than the raw CoQ10 in rats.

Overcoming the hydrophilicity of bacterial nanocellulose: Incorporation of the lipophilic coenzyme Q10 using lipid nanocarriers for dermal applications.

Although used in a wide range of medical and pharmaceutical applications, the potential of the natural biopolymer bacterial nanocellulose (BNC) as drug delivery system is by far not fully exploited. Particularly, the incorporation of lipophilic drugs is still considered as an unsolved task. In the present study, the homogeneous incorporation of the lipophilic coenzyme Q10 (CoQ10) into BNC was accomplished by several post-synthesis techniques utilizing different nanoemulsions and liposomes. All colloidal carriers were in the range of about 90-120 nm with negative zeta potentials and storage stabilities up to 30 days. The biphasic drug release profiles of loaded BNC were found to be dependent on the type of colloidal carrier and the loading technique. Favorable characteristics such as high mechanical stability and high loading capacity were retained after the incorporation of the lipophilic components. Penetration studies using excised porcine skin revealed CoQ10 distributions also in deeper skin layers dependent on the type of the colloidal carrier system. In conclusion, hydrophilic BNC could be loaded with water-insoluble drugs as shown for the model drug CoQ10 by the use of lipidic colloidal carriers which offers new possibilities of application in pharmacy and medicine.

Coenzyme Q10 supplementation: Efficacy, safety, and formulation challenges.

World population growth and aging are posing unprecedented challenges in sustaining the health of 9.1 billion people that will be occupying the planet by 2050. Although noncommunicable diseases such as cardiovascular and neurodegenerative diseases, cancer, and diabetes are among the top 10 global causes of death, they can be prevented by risk factor reduction, early detection, and adequate treatment. Since a healthy diet along with dietary supplementation could play an important role to reduce morbidity and cut off its associated health care costs, research in the food and nutrition area is required to find solutions to global challenges affecting health. As a result of the healthy living trend, dietary supplements category is growing fast, leading to an urgent need for dietitians, physicians, and policy makers to broaden the scientific evidence on the efficacy and safety of a wide range of active ingredients. Coenzyme Q10 (CoQ10), as the third most consumed dietary supplement, and as a potential candidate for the treatment of various noncommunicable diseases that are among the global top 10 causes of death, has gained interest over years. Scientific evidence regarding mainly CoQ10 efficacy and safety, as well as formulation challenges, is addressed in this review.

Coenzyme Q10: Novel Formulations and Medical Trends.

The aim of this review is to shed light over the most recent advances in Coenzyme Q10 (CoQ10) applications as well as to provide detailed information about the functions of this versatile molecule, which have proven to be of great interest in the medical field. Traditionally, CoQ10 clinical use was based on its antioxidant properties; however, a wide range of highly interesting alternative functions have recently been discovered. In this line, CoQ10 has shown pain-alleviating properties in fibromyalgia patients, a membrane-stabilizing function, immune system enhancing ability, or a fundamental role for insulin sensitivity, apart from potentially beneficial properties for familial hypercholesterolemia patients. In brief, it shows a remarkable amount of functions in addition to those yet to be discovered. Despite its multiple therapeutic applications, CoQ10 is not commonly prescribed as a drug because of its low oral bioavailability, which compromises its efficacy. Hence, several formulations have been developed to face such inconvenience. These were initially designed as lipid nanoparticles for CoQ10 encapsulation and distribution through biological membranes and eventually evolved towards chemical modifications of the molecule to decrease its hydrophobicity. Some of the most promising formulations will also be discussed in this review.

Investigation of ex vivo Skin Penetration of Coenzyme Q10 from Microemulsions and Hydrophilic Cream.

INTRODUCTION: Coenzyme Q10 (CoQ10) has been widely used in topical and cosmeceutical products due to its cutaneous antioxidant and energizer effects. CoQ10 is found in a higher concentration in the epidermis compared to dermis. The epidermal level of CoQ10 can be reduced due to several factors such as skin UV irradiation and photoaging. Various dermal nano-formulations have been investigated to overcome the skin barrier and enhance the poor penetration of CoQ10. The nanocarriers are designed to target and concentrate the CoQ10 in the viable epidermis. Most of these studies, however, failed to show the depth and extent of penetration of CoQ10 from the various carrier systems. OBJECTIVE: The distribution of CoQ10 across the various skin layers has to be shown using skin slices representing the different skin layers. METHODS: To realize this objective, a sensitive and selective HPLC method was developed and validated for the quantification of CoQ10 in the different skin slices. The method applicability to skin penetration (using excised human skin) as well as stability studies was investigated using CoQ10-loaded lecithin-based microemulsion (ME) and hydrophilic cream formulations. RESULTS: It could be shown that the highest concentration of CoQ10 in the viable epidermis, the target skin layer for CoQ10, was observed after application of the CoQ10 in the hydrophilic cream. This cream contains 10% of 2-ethylhexyl laurate which works obviously as a penetration enhancer for CoQ10. In contrast, the penetration of CoQ10 was lower from the ME. Just in the deeper dermis, a certain amount of CoQ10 could be detected. CONCLUSIONS: The HPLC method quantified the trace quantities of the CoQ10 distributed across the various skin layers and, hence, can be used to investigate the skin penetration of CoQ10 from various dermal standard and nano-formulations.

Synthesis and controlled drug delivery studies of a novel Ubiquinol-Polyethylene glycol-Vitamin E adduct.

CoQ10 and Vitamin E are used in medicinal applications, but they are both lipophilic molecules and the poor solubility in aqueous media results in an inefficient administration, poor bioavailability and potential toxicity. A mixed conjugate Ubiquinol-Polyethylene glycol-Vitamin E was synthesized and characterized to improve the bioavailability of CoQ10 and Vitamin E. The synthesized mixed PEG conjugate was characterized by 1H NMR spectroscopy and MALDI spectrometry. The in vitro release of the conjugate was measured at various pH conditions and in human plasma and the evaluation of free CoQ10 and Vitamin E were also conducted. The obtained results demonstrated that more CoQ10 and Vitamin E were released from PEG conjugate at pH 7.4 and in plasma within the 24 h. The antioxidant activity evaluation was carried out by DPPH assay. Our results indicated that the chemical modification after esterification with PEG of the two drugs Ubiquinol and Vitamin E doesn't significantly affected their antioxidant potential.

Transport via Niemann-Pick C1 Like 1 contributes to the intestinal absorption of ubiquinone.

Ubiquinone, which is a component in the electron-transport systems of mitochondria, is essential for various activities related to energy metabolism, but the detailed absorption mechanism of ubiquinone is not clear. On the other hand, Niemann-Pick C1 Like 1 (NPC1L1) is involved in the intestinal absorption of fat-soluble components such as cholesterol. In this study, we investigated whether the intestinal absorption of ubiquinone was transported by NPC1L1 as is cholesterol. In this study, coenzyme q10 (CoQ10) and coenzyme q9 (CoQ9) were used as models of ubiquinone. The transport activity of ubiquinone was increased significantly in NPC1L1-overexpressed Madin-Darby canine kidney (MDCK) cells compared with that in pMAM2-BSD vector-transfected MDCK cells and the uptake of ubiquinone was decreased in the presence of ezetimibe, an inhibitor of NPC1L1. These results indicate that NPC1L1 mediates the transport of ubiquinone. Furthermore, to clarify the effect of NPC1L1 on the intestinal absorption of CoQ10, emulsified CoQ10 was orally administered to Wistar rats, and the plasma concentration was measured. The plasma concentration of CoQ10 was significantly decreased by coadministration of ezetimibe and CoQ10 compared to that with administration of only CoQ10. This result indicates that the intestinal absorption of CoQ10 is mediated by NPC1L1.

Bioavailability of coenzyme Q10 loaded in an oleogel formulation for oral therapy: Comparison with a commercial-grade solid formulation.

Coenzyme Q10 (CoQ10) is essential in mitochondrial bioenergetics and is a potent endogenous antioxidant. Low CoQ10 levels are associated with neurodegenerative, metabolic, muscular and cardiovascular disorders. Early treatment with high doses (5-50 mg/kg/day) demonstrated to limit the onset and progression of neuropathology. Recently, we developed an oleogel matrix able to support a high dose of oil-dissolved CoQ10, easy to swallow by CoQ10-deficient patients who suffer from secondary dysphagia. In the present study, we evaluated the bioavailability of oleogel-dissolved CoQ10 and plasma antioxidant status in healthy adults in single-dose and repeated-dose studies. The single-dose study demonstrated that, in terms of CoQ10 bioavailability, 1 g CoQ10/5g oleogel-disk was equivalent to the solid form (1 g CoQ10/three 00-size-capsules), whereas the repeated-dose study (14-days-administration) demonstrated a significantly higher increase in plasma CoQ10 when administered through the oleogel, which could be compatible with the levels necessary to achieve an adequate therapeutic response. Also, a trend to a higher plasma apparent half-life (greater than24 h) was observed for the oleogel-loaded-CoQ10. In conclusion, the oleogel matrix does not compromise the oil-dissolved CoQ10 bioavailability and can prevent the non-adherence to this vital supplementation in patients with high CoQ10 requirements. No significant variation in the plasma antioxidant status (vitamins A, E and C, glutathione and TBARs) was observed.

Comparative Bioavailability of Different Coenzyme Q10 Formulations in Healthy Elderly Individuals.

Coenzyme Q10 (CoQ10) plays a central role in mitochondrial oxidative phosphorylation. Several studies have shown the beneficial effects of dietary CoQ10 supplementation, particularly in relation to cardiovascular health. CoQ10 biosynthesis decreases in the elderly, and consequently, the beneficial effects of dietary supplementation in this population are of greater significance. However, most pharmacokinetic studies have been conducted on younger populations. The aim of this study was to investigate the single-dose bioavailability of different formulations of CoQ10 in a healthy geriatric population. A randomized, three-period, crossover bioavailability study was conducted on 21 healthy older adults (aged 65-74). The treatment was a single dose with a one-week washout period. Three different formulations containing the equivalent of 100 mg of CoQ10 were used: Q10Vital® water-soluble CoQ10 syrup (the investigational product-IP); ubiquinol capsules (the comparative product-CP); and ubiquinone capsules (the standard product-SP). Ubiquinone/ubiquinol was followed in the plasma for 48 h. An analysis of the ratio of the area under the baseline-corrected concentration curve (ΔAUC48) for total CoQ10 and a comparison to SP yielded the following: The bioavailability of CoQ10 in the IP was 2.4-fold higher (95% CI: 1.3-4.5; p = 0.002), while the bioavailability of ubiquinol (CP) was not significantly increased (1.7-fold; 95% CI: 0.9-3.1, p = 0.129). No differences in the redox status of the absorbed coenzyme Q10 were observed between formulations, showing that CoQ10 appeared in the blood mostly as ubiquinol, even if consumed as ubiquinone.

Coenzyme Q10.

Coenzyme Q10 (CoQ10) is among the most widely used dietary and nutritional supplements on the market. CoQ10 has several fundamental properties that may be beneficial in several clinical situations. This article reviews the pertinent chemical, metabolic, and physiologic properties of CoQ10 and the scientific data and clinical trials that address its use in two common clinical settings: statin-associated myopathy syndrome (SAMS) and congestive heart failure (CHF). Although clinical trials of CoQ10 in SAMS have conflicting conclusions, the weight of the evidence, as seen in meta-analyses, supports the use of CoQ10 in SAMS overall. In CHF, there is a lack of large-scale randomized clinical trial data regarding the use of statins in patients receiving contemporary treatment. However, one relatively recent randomized clinical trial, Q-SYMBIO, suggests an adjunctive role for CoQ10 in CHF. Recommendations regarding the use of CoQ10 in these clinical situations are presented.

A carbohydrate polymer is a critical variable in the formulation of drug nanocrystals: a case study of idebenone.

Objective: Stabilizers, especially carbohydrate polymers, have been shown to be necessary for the stabilization of drug nanocrystals. However, the impacts of select stabilizers on the in vitro and in vivo efficacy of therapeutics have rarely been reported. The aim of this study was to evaluate the importance of stabilizers in the formulation of drug nanocrystals.Research design and methods: Idebenone nanocrystals (IDBNC) stabilized by various stabilizers were formulated using a milling method. The in vitro dissolution profiles in water and in situ absoprtion were compared. Finally, an in vivo pharmacokinetic study was performed.Results: The IDBNC profiles were found to have acceptable sizes and similar morphology and crystallinity. The dissolution profiles of IDBNC stabilized by different stabilizers were notably different, indicating the critical influence of stabilizers on the release rate of IDB. The Soluplus-stabilized IDBNC (IDBNC400 nm/Soluplus) achieved better absorption than HPMC stabilized IDBNC (IDBNC400 nm/HPMC). The pharmacokinetic study demonstrated that Soluplus-stabilized IDBNC had preferable kinetics, with an AUC0-24h of IDBNC400 nm/Soluplus (3.08-fold relative to IDB suspension), compared to IDBNC400 nm/HPMC (1.88-fold).Conclusions: Choice of stabilizer plays an important role in the formulation of IDBNC. We anticipate that the role of stabilizers in the pharmacokinetic disposition of IDBNC has significant implications for a wide range of other drug crystal formulations.

A New Food-grade Coenzyme Q10 Formulation Improves Bioavailability: Single and Repeated Pharmacokinetic Studies in Healthy Volunteers.

BACKGROUND: Coenzyme Q10 is a fundamental endogenous factor involved in cell energy production that shows protective properties in oxidative stress, mainly in skeletal and heart muscle. Coenzyme Q10 supplementation appears to benefit athletes in strenuous training and in the elderly, demonstrating ant-inflammatory properties by reducing inflammatory cytokines. Improved absorption of coenzyme Q10 via a new delivery system would represent an important step forward in the use of coenzyme Q10 as a dietary supplement. OBJECTIVE: The aim of the study was to evaluate the solubility and oral absorption in human healthy volunteers of a new food grade coenzyme Q10 phytosome formulation. METHODS: Solubility studies were performed in vitro in simulated gastrointestinal fluids; human studies were conducted in healthy volunteers to evaluate oral absorption in a Single dose study, in comparison with the coenzyme Q10 capsules, and in a repeated study at two increasing doses. RESULTS: The highest solubility shown by coenzyme Q10 phytosome in simulated intestinal fluids results in an improvement in oral absorption of coenzyme Q10 in healthy volunteers, three times more than the coenzyme Q10 according to AUC (area under the time/concentration curve) values. When two increasing doses (one and two capsules) were administered to healthy volunteers within a two-week schedule, the plasmatic levels of coenzyme Q10 resulted in 0.864±0.200 µg/ml (Mean±S.D.+41%) and 1.321±0.400 µg/ml (+116%), respectively versus baseline (0.614±0.120 µg/ml one capsule, 0.614±0.160 µg/ml two capsules). This detected dose-related bioavailability of coenzyme Q10 phytosome was even observed with no alterations in vital signs, neither in the physical examination nor in ECG, and no changes of clinical and biochemical parameters were observed. CONCLUSION: These findings, taken together, support the safety profile and significantly improved coenzyme Q10 oral absorption in humans with this new phytosome delivery formulation.

Green Formulation of Triglyceride/Phospholipid-Based Nanocarriers as a Novel Vehicle for Oral Coenzyme Q10 Delivery.

This study was aimed to develop a novel nanocarrier for coenzyme Q10 (CoQ10) by a green process that prevented the use of surfactants and organic solvents. Triglyceride/phospholipid-based nanocarriers were developed through high-pressure homogenization (an industrial feasible process), and a 25-1 fractional factorial design was adopted to assess the influences of formulation variables on the considered responses, including vesicle size, entrapment efficiency, loading capacity, and solubility of the vehicles in simulated gastrointestinal fluids. The optimized formulation was further in-depth characterized in terms of morphology, release behavior, biocompatibility (Caco-2 cell cytotoxicity and histological examination), thermal behavior, and Fourier transform infrared analysis. Optimal nanocarriers were found to have mean particle size of 75 nm, narrow particle distribution, and CoQ10 entrapment of 95%. The optimized formulation was stable upon incubation in simulated gastrointestinal fluids without considerable leakage of cargo, which was in agreement with their sustained release behavior. Microscopic observations also confirmed nanosized nature of the vesicles and revealed their spherical shape. Moreover, toxicity evaluations at the cellular and tissue levels revealed their nontoxic nature. In conclusion, triglyceride/phospholipid-based nanocarriers proved to be a green safe vehicle for delivery of CoQ10 with industrial-scale production capability and could provide a new horizon for delivery of hydrophobic nutraceuticals. PRACTICAL APPLICATION: Green nanostructure formulation approaches have recently gained tremendous attraction for their safe profile especially when it comes to supplements, which are generally recommended for daily use. However, their sufficient association with cargoes and industrial-scale production have remained considerable challenges. This study focuses on the development of lipid-based nanocarriers for CoQ10 by an industrial feasible process that prevents the use of any surfactants or organic solvents.

Carrier-Free Supramolecular Hydrogel Composed of Dual Drugs for Conquering Drug Resistance.

The resistance of tumor cells to anticancer drugs has become one of the principal causes of the failure in clinical chemotherapy. To overcome this issue, developing feasible drug delivery systems for effective cancer therapy is urgently needed. In this work, we construct an amphiphilic drug self-delivery system consisting of Taxol and tyroservatide (YSV) to overcome drug resistance. The carrier-free supramolecular hydrogel composed of nanofibers is formed by the involved ester bond self-hydrolysis process, which has high drug loading efficiency and facilitates the delivery of both the hydrophobic Taxol and hydrophilic YSV. Because of the dual inhibitory function of YSV on histone deacetylase and P-glycoprotein, an improved combinational anticancer effect of the molecule against drug-resistant tumor cells in vitro is achieved. Furthermore, the designed drug self-delivery system exhibited enhanced antitumor efficiency and favorable biocompatibility in vivo when administered by tail vein injection. Our study provides a new strategy for fabricating a carrier-free supramolecular hydrogel to overcome drug resistance, which might open up an alternative avenue for the tumor combinational therapy.

Influence of omega fatty acids on skin permeation of a coenzyme Q10 nanoemulsion cream formulation: characterization, in silico and ex vivo determination.

Objective: The aim of this study was to develop a coenzyme Q10 nanoemulsion cream, characterize and to determine the influence of omega fatty acids on the delivery of coenzyme Q10 across model skin membrane via ex vivo and in silico techniques. Methods: Coenzyme Q10 nanoemulsion creams were prepared using natural edible oils such as linseed, evening primrose, and olive oil. Their mechanical features and ability to deliver CoQ10 across rat skin were characterized. Computational docking analysis was performed for in silico evaluation of CoQ10 and omega fatty acid interactions. Results: Linseed, evening primrose, and olive oils each produced nano-sized emulsion creams (343.93-409.86 nm) and exhibited excellent rheological features. The computerized docking studies showed favorable interactions between CoQ10 and omega fatty acids that could improve skin permeation. The three edible-oil nanoemulsion creams displayed higher ex vivo skin permeation and drug flux compared to the liquid-paraffin control cream. The linseed oil formulation displayed the highest skin permeation (3.97 ± 0.91 mg/cm2) and drug flux (0.19 ± 0.05 mg/cm2/h). Conclusion: CoQ10 loaded-linseed oil nanoemulsion cream displayed the highest skin permeation. The highest permeation showed by linseed oil nanoemulsion cream may be due to the presence of omega-3, -6, and -9 fatty acids which might serve as permeation enhancers. This indicated that the edible oil nanoemulsion creams have potential as drug vehicles that enhance CoQ10 delivery across skin.

The Use of a Microfluidic Device to Encapsulate a Poorly Water-Soluble Drug CoQ10 in Lipid Nanoparticles and an Attempt to Regulate Intracellular Trafficking to Reach Mitochondria.

A number of drugs that are currently on the market, as well as new candidates for drugs, are poorly water soluble. Because of this, a need exists to develop drug formulations that will permit the expanded use of such drugs. The use of liposomes and lipid nanoparticles for drug delivery has attracted attention as a technique for solubilizing molecules that are poorly water soluble, but this technique faces serious scale-up risks. In this study, we report on attempts to encapsulate Coenzyme Q10 (CoQ10) as a model of a poorly water-soluble drug in an MITO-Porter, a liposome for mitochondrial delivery using a microfluidic device (a CoQ10-MITO-Porter [µ]). The physical properties of the CoQ10-MITO-Porter [µ] including homogeneity, size, and preparation volume were compared with those for a CoQ10-MITO-Porter prepared by the ethanol dilution method (a CoQ10-MITO-Porter [ED]). In the case where a microfluidic device was used, a small-sized CoQ10-MITO-Porter was formed homogeneously, and it was possible to prepare it on a large scale. Intracellular observations using HeLa cells showed that the CoQ10-MITO-Porter [µ] was efficiently internalized by cells to reach mitochondria. These results indicate that the CoQ10-MITO-Porter [µ] represents a potential candidate for use in mitochondrial nanomedicine.

MitoQ ameliorates testis injury from oxidative attack by repairing mitochondria and promoting the Keap1-Nrf2 pathway.

Mitochondrial dysfunctions induced by oxidative stress could play a pivotal role in the development of testicular damage and degeneration, leading to impaired fertility in adulthood. MitoQ as mitochondria-targeted antioxidant has been used in many diseases for a long time, but its therapeutic effects on testicular injury 'have not been reported yet. Here, we examined the protective action mechanism of MitoQ on testicular injury from oxidative stress induced by triptolide (TP). Mice were orally administrated with MitoQ (1.3, 2.6 and 5 .2mg/kg, respectively) in a TP-induced model of testicular damage for 14 days. And then testis injuries were comprehensively evaluated in terms of morphological changes, spermatogenesis assessment, blood-testis barrier (BTB) integrity, and apoptosis. The results demonstrated MitoQ effectively increased testicular weight, maintained the integrity of BTB, protected microstructure of testicular tissue and sperm morphology by inhibition of oxidative stress. Further mechanism studies revealed that MitoQ markedly activates the Keap1-Nrf2 antioxidative defense system characterized by increasing the expression of Nrf2 and its target genes HO-1 and NQO1. Meanwhile, MitoQ upregulated the expression of mitochondrial dynamics proteins Mfn2 and Drp-1and exerted a protective effect on mitochondria. On this basis, the results from pharmacokinetic study indicated that the MitoQ could enter into testis tissues after oral administration in despite of the low absolute bioavailability, which provided the material basis for MitoQ in the treatment of testicular damage. More importantly, MitoQ reached mitochondria quickly and had an outstanding feature of mitochondria targeting in Sertoli cells. Therefore, these results provide information for the application of MitoQ against testicular injury diseases.

Bioavailability and Sustained Plasma Concentrations of CoQ10 in Healthy Volunteers by a Novel Oral Timed-Release Preparation.

Coenzyme Q10 (CoQ10) is a natural compound with potent antioxidant properties. Its provision through diet does not always allow adequate levels in the human body, and supplementation is often necessary. This bioavailability study intended to explore the plasma concentration levels of a novel CoQ10 oral preparation (COQUN®, Coenzyme Q10 Miniactives Retard 100 mg capsules) mimicking assumption on a regular basis. Twenty-four healthy adults tested a single dose of CoQ10 100 mg in one day to assess bioavailability. After a one week wash-out period, they were randomly assigned (1:1) to continuous administration for four weeks: Group A (n = 12) 100 mg once a day (OD); and Group B (n = 12) 100 mg twice a day (BID). During the single dose phase, Cmax was observed at 4 h, and the mean values of AUCt and Tmax were 8754 µg/mL·h and 4.29 h, respectively. The multiple dose phase showed increasing plasma levels up to 7 days after the start of administration, and sustained high concentrations during the all administration period. No relevant adverse events were reported. These results show that Miniactives® technology can release CoQ10 to allow high constant blood concentrations without a sharp decrease. This may be the first step of evidence for a potential new antioxidative treatment in human chronic diseases deserving high CoQ10 levels.

PET imaging of 11C-labeled coenzyme Q10: Comparison of biodistribution between [11C]ubiquinol-10 and [11C]ubiquinone-10.

Coenzyme Q10 (CoQ10) plays a key role not only as an essential electron carrier in the mitochondrial electron transport chain, but also as an antioxidant to protect cells from oxidative stress. CoQ10 supplementation is expected to be effective for a variety of diseases. The predominant forms of CoQ10 are the ubiquinol-10 (reduced form) and ubiquinone-10 (oxidized form). Both forms of CoQ10 supplements are commercially available, however, their kinetic difference is still unclear. In order to conduct in vivo analysis of the kinetics of ubiquinol-10 and ubiquinone-10, we succeeded in synthesizing 11C-labeled ubiquinol-10 ([11C]UQL) and ubiquinone-10 ([11C]UQN), respectively. In the present study, we aimed to investigate the kinetics of [11C]UQL and [11C]UQN, both of which were administered via the tail vein of 8-week-old male Sprague-Dawley rats. Whole-body positron emission tomography (PET) imaging was performed to follow the time course of accumulation in the liver, spleen, brain, and other organs. Then, at the two typical time points at 20 or 90 min after injection, we conducted the biodistribution study. Various organs/tissues and blood were collected, weighed and counted with a gamma counter. Percent injected dose per gram of tissue (%ID/g) was calculated as the indicator of the accumulation of each compound. As the results, at both time points, %ID/g of [11C]UQL in the cerebrum, cerebellum, white adipose tissue, muscle, kidney, and testis were higher (P < 0.05) than that of [11C]UQN: at 90-min time point, %ID/g of [11C]UQL in the brown adipose tissue was higher (P < 0.05) than that of [11C]UQN: on the contrary, %ID/g of [11C]UQL in the spleen was lower (P < 0.05) than that of [11C]UQN at 90 min. In a separate study of the metabolite analysis in the plasma, UQL injected into the tail vein of rats was almost unchanged during the PET scanning time, but UQN was gradually converted to the reduced form UQL. Therefore, the uptake values of UQL into the tissues and organs were rather accurate but those of UQN might be the sum of UQN uptake and partly converted UQL uptake. These studies suggested that the accumulation level of administered CoQ10 differs depending on its redox state, and that CoQ10 redox state could be crucial for optimization of the effective supplementation.