Coenzyme Q10 Formulations Research Articles

Preparation and characterization of a solid dispersion formulation of coenzyme Q10 loaded with protamine: an efficient and novel strategy to enhance bioavailability and stability

Coenzyme Q10 (CoQ10) is an endogenous, lipophilic quinone compound that functions as an electron carrier in the mitochondrial respiratory chain and plays a pivotal role in cell metabolism. Despite its numerous important physiological functions, the practical application of CoQ10 is limited due to its high molecular weight, poor water solubility, photolability, chemical instability, and low bioavailability. To overcome these challenges, we developed a solid dispersion formulation of protamine loaded CoQ10 (CoQ10/Pr) using an efficient mechanochemical technology without solvents. Protamine was used as carrier and poloxamer 188 as solubilizer, while butylated hydroxytoluene (BHT) and micro powder silica gel were utilized as stabilizers and lubricants. The optimal ball milling condition to prepare CoQ10/Pr was at 100 r/min for 4 hours. The treated CoQ10/Pr has exhibited rapid-release properties, with significantly enhanced water solubility by 392,000 times, and bioavailability by 0.68 times. Furthermore, the treated CoQ10/Pr became resistant to moisture, high temperature and strong light, which makes it suitable for long-term storage. The molecular docking suggested that the solubilization mechanism of CoQ10 was closely associated with the encapsulation and complexation of protamine, as well as the formation of an intermolecular complex through hydrogen bond between CoQ10 and arginine residues on protamine. In summary, the CoQ10 solid dispersion formulation enjoys advantages such as excellent water solubility, stability, bioavailability, and low cost. This formulation also meets the stringent quality requirements of products in the food, cosmetic, and health industries. It offers dual benefits in both theoretical research and industrial development.

CoQ10Phytosomes Improve Cellular Ubiquinone Uptake in Skeletal Muscle Cells: An Ex Vivo Study Using CoQ10-Enriched Low-Density Lipoproteins Obtained in a Randomized Crossover Study.

Coenzyme Q10 (CoQ10) bioavailability in vivo is limited due to its lipophilic nature. Moreover, a large body of evidence in the literature shows that muscle CoQ10 uptake is limited. In order to address cell specific differences in CoQ uptake, we compared cellular CoQ10 content in cultured human dermal fibroblasts and murine skeletal muscle cells that were incubated with lipoproteins from healthy volunteers and enriched with different formulations of CoQ10 following oral supplementation. Using a crossover design, eight volunteers were randomized to supplement 100 mg/daily CoQ10 for two weeks, delivered both in phytosome form (UBQ) as a lecithin formulation and in CoQ10 crystalline form. After supplementation, plasma was collected for CoQ10 determination. In the same samples, low density lipoproteins (LDL) were extracted and normalized for CoQ10 content, and 0.5 µg/mL in the medium were incubated with the two cell lines for 24 h. The results show that while both formulations were substantially equivalent in terms of plasma bioavailability in vivo, UBQ-enriched lipoproteins showed a higher bioavailability compared with crystalline CoQ10-enriched ones both in human dermal fibroblasts (+103%) and in murine skeletal myoblasts (+48%). Our data suggest that phytosome carriers might provide a specific advantage in delivering CoQ10 to skin and muscle tissues.

Antitumor Immunotherapy of Sialic Acid and/or GM1 Modified Coenzyme Q10 Submicron Emulsion.

Immunotherapy is a novel therapeutic approach for controlling and killing tumor cells by stimulating or reconstituting the immune system, among which T cells serve as immune targets. Herein, we used coenzyme Q10 (CoQ10), which has both immune activation and avoids adverse reactions, as a model drug and developed four CoQ10 submicron emulsions modified with sialic acid (SA) and/or monosialotetrahexosyl ganglioside (GM1). On the one hand, SA interacts with L-selectins on the surface of T cells after entering the circulatory system, leading to activation of T cells and enhancement of antitumor immune responses. On the other hand, owing to its immune camouflage, GM1 can prolong the circulation time of the preparation in the body, thereby increasing the accumulation of the drug at the tumor site. In vitro and in vivo experiments showed that SA-modified preparations exhibited stronger immune activation and inhibition of tumor proliferation. Pharmacokinetic experiments showed that GM1-modified preparations have longer circulation times in vivo. However, SA and GM1 co-modification did not produce a synergistic effect on the preparation. In conclusion, the SA-modified CoQ10 submicron emulsion (Q10-SE) showed optimal antitumor efficacy when administered at a medium dose (6mg CoQ10 kg-1). In this study, the submicron emulsion model was used as a carrier, and the tumor-bearing mice were used as animal models. In addition, CoQ10 submicron emulsion was modified with SA-CH with active targeting function and/or GM1 with long-circulation function to explore the antitumor effects of different doses of CoQ10 submicron emulsion, and to screen the best tumor immunotherapy formulations of CoQ10.

NON-INVASIVE INSTRUMENTAL EVALUATION OF COENZYME Q10 PHYTOSOME ON ENDOTHELIAL REACTIVITY IN HEALTHY NON-SMOKING YOUNG VOLUNTEERS: A RANDOMIZED, PLACEBO-CONTROLLED CROSS-OVER STUDY

Objective: The present study aimed to investigate the effect on endothelial reactivity and total antioxidant capacity (TAC) of either acute and chronic supplementation with coenzyme Q10 (CoQ10) phytosome in a sample of 20 healthy young not smoking subjects. Design and method: This was a double-blind, randomized, placebo-controlled, cross-over clinical trial. Enrolled subjects were adhering to a low-fat low-sodium Mediterranean diet for four weeks before being randomized to receive CoQ10 supplement or placebo. At baseline and on the day of crossover, the immediate acute effect of dietary supplementation with CoQ10 phytosome was assessed at baseline and two hours after receiving a double dose of either active treatment or placebo. Study’s participants received adequate doses of either CoQ10 phytosome or placebo to complete the one of two 4-week treatment sequences. The crossover to the second treatment was preceded by a 2-week wash-out period. Results: The immediate acute effect of dietary supplementation with CoQ10 phytosome on pulse volume (PV) was sustained in the actively treated group in comparison with placebo and the baseline (p < 0.05). Chronic supplementation of the tested pharmaceutical formulation of CoQ10 significantly improved mean arterial pressure and TAC compared to placebo and baseline values (p < 0.05 for both comparisons). In the actively treated group, the effect on dietary supplementation with CoQ10 phytosome on PV was also sustained when compared to the baseline (P < 0.05). Conclusions: In conclusion, CoQ10 phytosome exerts beneficial effects on endothelial reactivity in healthy young subjects. Further studies are needed that confirms our observations in the long term by directly comparing different CoQ10 pharmaceutical formulations.

Noninvasive instrumental evaluation of coenzyme Q10 phytosome on endothelial reactivity in healthy nonsmoking young volunteers: A double-blind, randomized, placebo-controlled crossover clinical trial.

Coenzyme Q10 (CoQ10 ) is a natural antioxidant compound that prevents the vascular damage induced by free radicals and the activation of inflammatory signaling pathways. Supplementation with CoQ10 is safe though its bioavailability is generally low, as far as variable depending on the pharmaceutical form of preparation. Recently, the development of phytosome technology has improved the bioavailability of CoQ10 and definitely facilitated its effective use in clinical practice. The present double-blind, randomized, placebo-controlled, crossover clinical study aimed to investigate the effect on endothelial reactivity and total antioxidant capacity (TAC) of either acute and chronic supplementation with CoQ10 phytosome in a sample of 20 healthy young nonsmoking subjects. CoQ10 phytosome supplementation acutely improved endothelial reactivity in comparison with baseline and placebo (+4.7% ± 0.9% vs. -0.1%± 0.3% p< 0.05). Middle-term supplementation of the tested pharmaceutical formulation of CoQ10 significantly improved mean arterial pressure (-2.2± 1.1 mmHg vs. 0.2± 0.7 mmHg, p< 0.05 vs. placebo) and TAC (+29.6% ± 3.2% vs. +1.9% ± 0.8%, p< 0.05 vs. placebo). Endothelial reactivity improved compared with baseline following middle-term dietary supplementation with CoQ10 phytosome (+5.7% ± 1.1%, p< 0.05).

Evaluation of the Efficacy of Coenzyme Q10 in the Management of Chronic Periodontitis: A Clinical Study

Abstract Aim The present study was aimed to clinically evaluate the effectiveness of coenzyme Q10 (CoQ10) in the management of chronic periodontitis. Materials and Methods A total of 60 patients aged between 30 and 60 years with bleeding on probing and probing pocket depth (PPD) of 3 to 5 mm were selected and divided into three groups, with group I receiving scaling and root planing, group II CoQ10 formulation for 6 weeks, and group III receiving both scaling and root planning, followed by coenzyme Q10 administration for 6 weeks. PPD, relative attachment level (RAL), and gingival index were recorded in all the groups at baseline, 6 weeks, and 3 months, respectively. The data was statistically analyzed using Kruskal–Wallis, Mann–Whitney, and Wilcoxon signed rank tests. Result Intragroup comparison showed statistically significant difference (p ≤ 0.05) between the clinical parameters of all the groups at all time intervals, whereas intergroup comparison of all the parameters showed high statistically significant difference (p ≤ 0.001) in group III at various time intervals followed by group I and group II. Conclusion It was concluded from the study that CoQ10 is a useful adjunct in treating chronic periodontitis by boosting the host resistance to periodontal disease.

Coenzyme Q10 Phytosome Formulation Improves CoQ10 Bioavailability and Mitochondrial Functionality in Cultured Cells.

Coenzyme Q10 (CoQ10) is a lipid-soluble molecule with a dual role: it transfers electrons in the mitochondrial transport chain by promoting the transmembrane potential exploited by the ATPase to synthesize ATP and, in its reduced form, is a membrane antioxidant. Since the high CoQ10 hydrophobicity hinders its bioavailability, several formulations have been developed to facilitate its cellular uptake. In this work, we studied the bioenergetic and antioxidant effects in I407 and H9c2 cells of a CoQ10 phytosome formulation (UBIQSOME®, UBQ). We investigated the cellular and mitochondrial content of CoQ10 and its redox state after incubation with UBQ. We studied different bioenergetic parameters, such as oxygen consumption, ATP content and mitochondrial potential. Moreover, we evaluated the effects of CoQ10 incubation on oxidative stress, membrane lipid peroxidation and ferroptosis and highlighted the connection between the intracellular concentration of CoQ10 and its antioxidant potency. Finally, we focused on the cellular mechanism that regulates UBQ internalization. We showed that the cell lines used in this work share the same uptake mechanism for UBQ, although the intestinal cell line was less efficient. Given the limitations of an in vitro model, the latter result supports that intestinal absorption is a critical step for the oral administration of Coenzyme Q10 formulations.

Evaluation of wound healing potential of new composite liposomal films containing coenzyme Q10 and d-panthenyl triacetate as combinational treatment

Conventional formulations can not achieve wound healing efficiently and fail to accelerate wound regeneration. To overcome these problems, it was planned to develop nanoformulations that perform a positive effect on the wound healing duration and are suitable for topical use. In this study, liposomal film formulations that encapsulated d-panthenyl triacetate (PTA) and coenzyme Q10 (CoQ10) were optimized by using response surface methodology (RSM) and were analyzed for their wound healing efficacy and cytotoxicity on fibroblast (CCD1079 Sk) and keratinocyte (HEKa) cells. Swelling index, puncture strength, and puncture deformation values, which were choosen as dependent variables for the liposomal film formulation were found as 556.9% ± 21.3, 3.98 ± 0.98 N/mm2, and 6.57% ± 1.12, respectively. Cumulative release of 65.32% for PTA and 12.23% for CoQ10 was obtained after 24 hours of in vitro release study in sink conditions. The in vitro cytotoxicity and wound healing assay results suggested that optimum formulation could be used safely on fibroblast and keratinocyte cells and provided wound closure entirely after 24 h. Consequently, the optimum liposomal film containing PTA and CoQ10 formulations could be proposed as an innovative approach in wound healing treatment, considering their release, mechanical properties, stability, and effectiveness.

Chitosan-coated liposome-containing carbamazepine and coenzyme Q10: design, optimization and evaluation

Conventional formulations cannot sufficiently control seizures and influence on cognitive corruption and oxidative stress with chronic usage in patients with epilepsy. To defeat this issue, it was planned to develop polymeric liposome formulations that are using for their bioavailability and enhancer impact in oral epilepsy treatment. In this study, chitosan-coated liposomal formulations that encapsulate carbamazepine (CBZ) and coenzyme Q10 (CoQ10) were prepared and optimized by utilizing response surface methodology (RSM). Encapsulation efficiencies of CBZ and CoQ10, which were chosen as dependent variables for optimized chitosan-coated liposomal formulations were determined as 76.13%±2.34% and 82.36%±3.15%, respectively. Narrow size distribution was provided with an average size of 187.1 ± 2.35 nm, while a spherical and uniform shape was approved with transmission electron microscopy analyses. Cumulative release of 78.23% for CBZ and 27.12% for CoQ10 was obtained after 24 hours of in-vitro release study in sink conditions. Physical stability analyses demonstrated that optimum liposomes were convenient for storage at 5 ± 3 °C for at least 90 days. As a result, optimum chitosan-coated liposome containing CBZ and CoQ10 formulations could be suggested as a hopeful approach concerning their release, particle size, high encapsulation efficiency and stability for the treatment of epilepsy.

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.

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

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. 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. 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. 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. These findings, taken together, support the safety profile and significantly improved coenzyme Q10 oral absorption in humans with this new phytosome delivery formulation.

Pharmacokinetic Study on Three Formulations of Coenzyme Q10 With Different Carriers

Pharmacokinetic Study on Three Formulations of Coenzyme Q10 With Different Carriers

The Plasma Bioavailability of Coenzyme Q10 Absorbed from the Gut and the Oral Mucosa.

Coenzyme Q10 (CoQ10) has a central role in the generation of cellular bioenergy and its regulation. The hydrophobicity exhibited by the CoQ10 molecule leads to reports of poor absorption profiles, therefore, the optimization of formulations and modes of delivery is an ever-evolving therapeutic goal. The aim of this study was to investigate different CoQ10 formulations. The article summarizes the findings from an Australian comparative study involving adults administered CoQ10 through different oral delivery platforms. A total of 11 participants (six males and five females) voluntarily participated in a comparative clinical study of three different CoQ10 formulations across a six-week period, completing 198 person-hours of cumulative contribution equivalent to n = 33 participation. All of the eligible participants (n = 11) administered the three formulations blinded from who the commercial supplier of the formulation was and from what the chemical form of the CoQ10 was that was being administered. The dosing between the CoQ10 preparations were dispensed sequentially and were administered following three-week washouts. Three commercial preparations were tested, which included the following: formulations with capsules each containing ubiquinol and ubiquinone (150 mg/capsule), and a liposome ubiquinone formulation (40 mg/mL at 2 actuations of the pump). A significant inter-subject variation in the plasma level of CoQ10 at baseline that was observed to increase with an increase in age. This trend persisted in the post administration of the different formulations. Furthermore, it was observed that the intestinal absorption and bioavailability of CoQ10 varied significantly in the plasma between subjects, irrespective of whether the ubiquinol or ubiquinone forms were administered. The administration of CoQ10 as a liposome for preparation showed the poorest response in bioavailability. Although the ubiquinol capsule form of CoQ10 was observed to have increased in the plasma versus the ubiquinone capsules and the ubiquinol liposome at the two-hour interval, the inter-subject variation was such that the difference was not significant (p > 0.05). All of the CoQ10 formulations showed no further increases in their plasma levels over the remaining study period (i.e., four hours). This study further concluded that the intestinal absorption of CoQ10 is highly variable and is independent of the molecular form administered. Furthermore, it also concludes that liposomes are not an effective vehicle for the oral administration of CoQ10, and as such, did not improve the oral mucosal/sublingual absorption and bioavailability of the molecule. Of interest was the observation that with the increasing subject age, there was an observed increase in the baseline plasma CoQ10 levels in the participants prior to dosing. It was posited that the increase in the baseline plasma levels of CoQ10 with an increase in age could be due to the loss of skeletal muscle mass, a result that still needs to be verified.

Ubisol-Q10 (a Nanomicellar Water-Soluble Formulation of CoQ10) Treatment Inhibits Alzheimer-Type Behavioral and Pathological Symptoms in a Double Transgenic Mouse (TgAPEswe, PSEN1dE9) Model of Alzheimer's Disease.

Alzheimer's disease (AD) is one of the most common neurodegenerative pathologies for which there are no effective therapies to halt disease progression. Given the increase in the incidence of this disorder, there is an urgent need for pharmacological intervention. Unfortunately, recent clinical trials produced disappointing results. Molecular mechanisms of AD are converging on the notion that mitochondrial dysfunction, oxidative stress, and accumulation of dysfunctional proteins are involved in AD pathology. Previously, we have shown that a water-soluble formulation of Coenzyme Q10 (Ubisol-Q10), an integral part of the electron transport chain, stabilizes mitochondria and prevents neuronal cell death caused by neurotoxins or oxidative stress both in vitro and in vivo. In this study, we evaluated the neuroprotective effects of Ubisol-Q10 treatment in double transgenic AD mice. In the present study, we report that providing Ubisol-Q10 in drinking water (at a dose of ∼6 mg/kg/day) reduced circulating amyloid-β (Aβ) peptide, improved long term memory, preserved working spatial memory, and drastically inhibited Aβ plaque formation in 18-month-old transgenic mice compared to an untreated transgenic group. Thus Ubisol-Q10 supplementation has the potential to inhibit the progression of neurodegeneration, leading to a better quality of life for humans suffering with AD.

Nebulized coenzyme Q10 nanosuspensions: A versatile approach for pulmonary antioxidant therapy

Coenzyme Q10 (CoQ10) is an antioxidant substance indicated as a dietary supplement which has been proposed as adjuvant in the treatment of cardiovascular disorders and cancer for its protective and immunostimulating activities. The aim of this work was the production by high-pressure homogenization, characterization and stability investigation of three different CoQ10 nanosuspensions designed to be administered to the lungs by nebulization.Three surfactants, i.e. lecithin, PEG32 stearate and vitamin-E TPGS, were selected to stabilize CoQ10 formulations. Preparations were identified as nanosuspensions (particle size in the range 35–60nm): the smallest particles were obtained with vitamin-E TPGS and denoted a core-shell structure. The CoQ10 delivered from a commercial air-jet nebulizer was in all the cases around 30% of the loaded dose. The nanosuspension containing PEG32 stearate presented the highest respirable fraction (70.6%) and smallest MMAD (3.02μm). Stability tests showed that the most stable formulation, after 90days, was the one containing vitamin-E TPGS, followed by the CoQ10-lecithin formulation. Interestingly, those formulations were demonstrated to be suitable also for nebulizers using other mechanisms of aerosol production such as ultrasound and vibrating mesh nebulizers.Studies focused on in vitro cellular toxicity of the formulations and their single components using A549 human lung cells showed no obvious cytotoxicity for the formulations containing lecithin and PEG 32 stearate. Vitamin-E TPGS alone was shown to be able to damage the plasma membrane, nevertheless, cell damage was decreased when vitamin-E TPGS was present in the formulation with CoQ10.

Does Coenzyme Q10 Supplementation Mitigate Statin-Associated Muscle Symptoms? Pharmacological and Methodological Considerations

Statin drugs markedly reduce low-density lipoprotein cholesterol and consequently the incidence of cardiac events. In approximately 5-10% of adults, these drugs are associated with a range of muscle side effects such as muscle pain, cramping and weakness. Reduction in mitochondrial coenzyme Q10 (CoQ10), or ubiquinone, has been proposed as a mechanism for these statin-associated muscle symptoms (SAMS), and thus various formulations of CoQ10 are marketed and consumed for the prevention and treatment of SAMS. However, data supporting the efficacy of CoQ10 are equivocal, with some studies showing that CoQ10 supplementation reduces the incidence and severity of SAMS and others finding no beneficial effects of supplementation. Methodological and pharmacological issues may confound interpretation of data on this topic. For example, many patients who report SAMS, such as those who have been enrolled in previous CoQ10 studies, may be experiencing non-specific (non-statin-associated) muscle pain. In addition, the effectiveness of oral CoQ10 supplementation to increase mitochondrial CoQ10 in human skeletal muscle is not well established. This manuscript will critically evaluate the published data on the efficacy of CoQ10 supplements in the prevention and treatment of SAMS.

Development of aqueous dispersions of Coenzyme Q10 for pulmonary delivery and the dynamics of active vibrating-mesh aerosolization

Coenzyme Q10 (CoQ10) is a poorly-water soluble compound that is being investigated for the treatment of carcinomas. The aim of this study was to investigate the feasibility of preparing phospholipid-stabilized dispersions of the anticancer agent for continuous pulmonary delivery using a vibrating-mesh nebulizer. We determined the physicochemical properties (drug particle size distribution in dispersion, zeta potential, surface tension, and rheology) and compared the aerosolization profiles (nebulization performance, aerodynamic drug deposition and total emitted dose) of dispersions of CoQ10 prepared with different phospholipids. The hydrodynamic sizes of the drug particles in dispersion were primarily in the submicron range, but formulations with drug particle sizes greater than the aperture size of the nebulizer presented superior aerosolization profiles. At high shear rates, certain formulations presented increased shear-thickening behavior, which was connected to a decrease in mass and drug output over time, and with decreased aerodynamic and geometric sizes. Other formulations presented shear-thinning behavior and showed similarly high drug depositions. In this investigation, we found that dispersed formulations of CoQ10 presented different in vitro performance for pulmonary delivery based on their rheological behavior. In conclusion, this characterization methodology provides an innovative approach to screen formulations of poorly-water soluble compounds for continuous (no clogging) active vibrating-mesh nebulization.

Coenzyme Q10 - A new player in the treatment of heart failure?

Coenzyme Q10 is the only endogenously synthesized lipid with a redox function which exhibits broad tissue and intracellular distribution in mammals. Beneficial effects of Coenzyme Q10 supplementation were observed in several age-related diseases including heart failure. CoQ10 (coenzyme Q10) level is significantly decreased in patients with this disease, which correlates with severity of clinical symptoms. Supplementation with various pharmaceutical formulations of CoQ10 improves impaired cardiac function and clinical course of heart failure. Current data from clinical trials indicate that CoQ10 can significantly reduce morbidity and mortality of heart failure patients in addition to guideline recommended pharmacotherapy.

Systematically optimized coenzyme q10-loaded novel proniosomal formulation for treatment of photo-induced aging in mice: characterization, biocompatibility studies, biochemical estimations and anti-aging evaluation

Environmental stress and advancing age is considered as the main cause of skin aging. However, environmental stress (especially UV radiations) accelerates the process of skin aging by manifolds. Coenzyme Q10 (CoQ10), an essential compound of cellular bioenergetics also acts as a strong antioxidant and protects the body against aging. High molecular weight and structure specific lipophilic nature of this molecule is a bottle neck in effective delivery through topical route. Preparation of a novel proniosomal (PN) gel formulation of CoQ10 employing systematic design of experiment (DoE) approach is a step ahead in transcending the constraints of the topical delivery. I-optimal mixture design was employed for systematic optimization of proniosomal formulation and evaluation of experimental data was performed for entrapment efficiency and in vitro release. Hydration of PN gel formulation with phosphate buffer (pH 7.5) results in submicron niosomes vesicles of spherical shape, which appeared dark against bright surroundings in TEM study. Animal skin was treated with UV radiations followed by treatment of PN gel CoQ10 and conventional CoQ10 present in a gel base. The effectiveness of the treatment was evaluated on the basis of biochemical estimation and histopathological studies. By using CoQ10 PN gel formulation, levels of superoxide dismutase (SOD), catalase (CA), glutathione (GSH) and total proteins were restored by 81.3%, 72.1%, 74.8 and 77.1%, respectively to that of control group. Histopathological studies revealed better protection of skin treated with CoQ10 PN gel compared to free CoQ10. Prepared PN gel was found undisturbing with the normal histology hence, tolerated by animal skin compare to conventional gel.

Nanomicellar formulation of coenzyme Q10 (Ubisol-Q10) effectively blocks ongoing neurodegeneration in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model: potential use as an adjuvant treatment in Parkinson's disease

Although the support for the use of antioxidants, such as coenzyme Q10 (CoQ10), to treat Parkinson's disease (PD) comes from the extensive scientific evidence, the results of conducted thus far clinical trials are inconclusive. It is assumed that the efficacy of CoQ10 is hindered by insolubility, poor bioavailability, and lack of brain penetration. We have developed a nanomicellar formulation of CoQ10 (Ubisol-Q10) with improved properties, including the brain penetration, and tested its effectiveness in mouse MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) model with the objectives to assess its potential use as an adjuvant therapy for PD. We used a subchronic MPTP model (5-daily MPTP injections), characterized by 50% loss of dopamine neurons over a period of 28 days. Ubisol-Q10 was delivered in drinking water. Prophylactic application of Ubisol-Q10, started 2 weeks before the MPTP exposure, significantly offset the neurotoxicity (approximately 50% neurons died in MPTP group vs. 17% in MPTP+ Ubisol-Q10 group by day 28). Therapeutic application of Ubisol-Q10, given after the last MPTP injection, was equally effective. At the time of intervention on day 5 nearly 25% of dopamine neurons were already lost, but the treatment saved the remaining 25% of cells, which otherwise would have died by day 28. This was confirmed by cell counts, analyses of striatal dopamine levels, and improved animals' motor skill on a beam walk test. Similar levels of neuroprotection were obtained with 3 different Ubisol-Q10 concentrations tested, that is, 30 mg, 6 mg, or 3 mg CoQ10/kg body weight/day, showing clearly that high doses of CoQ10 were not required to deliver these effects. Furthermore, the Ubisol-Q10 treatments brought about a robust astrocytic activation in the brain parenchyma, indicating that astroglia played an active role in this neuroprotection. Thus, we have shown for the first time that Ubisol-Q10 was capable of halting the neurodegeneration already in progress; however, to maintain it a continuous supplementation of Ubisol-Q10 was required. The pathologic processes initiated by MPTP resumed if supplementation was withdrawn. We suggest that in addition to brain delivery of powerful antioxidants, Ubisol-Q10 might have also supported subcellular oxidoreductase systems allowing them to maintain a favorable cellular redox status, especially in astroglia, facilitating their role in neuroprotection. Based on this data further clinical testing of this formulation in PD patients might be justifiable.