Delivery Of Coenzyme Q10 Research Articles

Advancing coenzyme Q10 delivery with plant protein-based nanoparticle-mediated nanosuspensions

Coenzyme Q10 (CoQ10) possesses significant health-promoting potential, yet its oral delivery encounters obstacles stemming from its distinctive physicochemical characteristics, such as poor solubility, sensitivity to environmental factors and low bioaccessibility. To overcome these challenges, we developed high-payload CoQ10 nanosuspensions (CQ@SPNP, CQ@RPNP, and CQ@WPNP) using plant-based protein nanoparticles (NPs) derived from soybean (SPNP), rice (RPNP), and walnut (WPNP). The nanosuspensions include spherical particles, characterized by small particle size (<230 nm), low polydispersity (PDI < 0.15), and a high zeta potential (<−44 mV). CoQ10 loading capacity exceeded 70.3 %, with an encapsulation efficiency of over 77.4 %. CoQ10 interacted with plant protein-based NPs via hydrophobic effect without losing its crystal structure. Moreover, SPNP, RPNP, and WPNP significantly increased the stability of CoQ10 nanosuspensions against light, heat, long-term storage, and in vitro digestion. In particular, CQ@WPNP exhibited the highest stability and CoQ10 bioaccessibility post-digestion. The observed increases in stability and bioaccessibility were closely related to the specific NPs utilized. This study highlights the potential of plant protein-based NPs in addressing challenges of CoQ10 delivery, offering a promising approach to improve its efficacy.

Activation of Mitochondrial Oxygen Consumption Rate by Delivering Coenzyme Q10 to Mitochondria of Rat Skeletal Muscle Cell (L6)

Numerous mitochondria are present in skeletal muscle cells. Muscle disease and aging impair mitochondrial functioning in the skeletal muscle. However, there have been few reports of therapeutic intervention via drug delivery to mitochondria owing to methodological difficulties. We surmised that mitochondrial activation is associated with improved skeletal muscle function. In this study, we attempted to activate the mitochondrial respiratory capacity in rat skeletal muscle cells (L6 cells) by delivering Coenzyme Q10 (CoQ10), a mitochondrial functional activator, to mitochondria using MITO-Porter, a nanoparticle that facilitates mitochondria-targeted drug delivery. Cellular uptake was confirmed by measuring the amount of fluorescence-modified MITO-Porter taken up by cells using flow cytometry. Intracellular dynamics of MITO-Porter was observed using confocal laser scanning microscopy. Mitochondrial function was assessed by measuring the mitochondrial oxygen consumption rate using an extracellular flux analyzer. The results indicated MITO-Porter-assisted delivery of CoQ10 to the mitochondria activated mitochondrial respiratory capacity in L6 cells. We believe that our results indicate the possibility of skeletal muscle therapy using mitochondrial drug delivery.

KOENZİM Q10 YÜKLÜ MİSEL İÇEREN KONTAKT LENSLERİN HAZIRLANMASI VE İN-VİTRO KARAKTERİZASYONU

Objective: Coenzyme Q10 (CoQ10) offers potential therapeutic benefits for ocular health, yet faces challenges of poor solubility and bioavailability when applied to the eye. This study aimed to enhance CoQ10 delivery using contact lenses by incorporating CoQ10-loaded polymeric micelles, using Pluronic F127 and solvent evaporation technique. Material and Method: Polymeric micelles encapsulating CoQ10 were produced via solvent evaporation with Pluronic F127. Commercial contact lenses were subsequently loaded with these micelles. Characterization of the loaded lenses included assessments of light transmittance, swelling behavior, and drug release profile under non-sink conditions, simulating the constraints of the ocular surface. Result and Discussion: The unloaded lenses exhibited a light transmittance of 91.78±3.29% and swelling percentage of 47.51±4.45% while micelle-loaded lenses demonstrated high light transmittance levels (95.31±0.80%), ensuring optical clarity. Swelling studies showed a slight increase in size to 48.1±4.4%. The lenses effectively encapsulated 403.6±21.8 µg of CoQ10. In vitro release profile exhibited controlled release over six hours, indicating potential for sustained drug delivery. These results highlight the feasibility of micelle-loaded contact lenses for efficient ocular drug delivery, warranting further exploration into their long-term effectiveness and safety.

TPGS and Doca dual-modified mesoporous silica nanoparticle-supported lipid bilayers enhance the efficient delivery and in vivo absorption of Coenzyme Q10

Coenzyme Q10 (CoQ10) has a wide range of nutraceutical functions and therapeutic values, nevertheless, its biomedical application as a health product or drug is hampered by the low absorption efficiency and bioavailability. In the present study, the hybrid mesoporous silica nanoparticle-supported lipid bilayers (LMSNs) as nanocarriers for CoQ10 are prepared by fusing the phospholipid membrane onto MSNs cores. Further, LMSNs are functionalized with d-α-tocopherol polyethylene glycol 1000 succinate (TPGS), deoxycholic acid (Doca) and chitosan (CS) sequentially, to obtain the TPGS-LMSNs and DCs-TPGS-LMSNs samples, respectively. MSNs, liposomes, and unmodified LMSNs are also prepared as controls. The results reveal that various nanocarriers have a high loading capacity for CoQ10, low cytotoxicity towards Caco-2 cells, and sustained release property in different pH mediums. In contrast to other nano-formulations, [email protected] show the higher cellular uptake efficiency and the resulting ROS inhibition effect, which can be taken up by cells via caveolae-mediated route, macropinocytosis, and unique bile acid uptake pathway mediated by ASBT. Efficient delivery of DC-TPGS-LMSNs is further illustrated by in vivo intestinal uptake and pharmacokinetics study, in which [email protected] exhibit higher absorption efficiency, longer circulation time, and more enhanced bioavailability than other formulations after oral administration. The results suggest that multifunctional LMSNs might be the potent candidate for CoQ10 delivery, and the findings will contribute to the rational design of novel drug delivery vehicles.

Delivery of coenzyme Q10 with mitochondria-targeted nanocarrier attenuates renal ischemia-reperfusion injury in mice

Ischemia-reperfusion (I/R) injury causes high morbidity, mortality, and healthcare costs. I/R induces acute kidney injury through exacerbating the mitochondrial damage and increasing inflammatory and oxidative responses. Here, we developed the mitochondria-targeted nanocarrier to delivery of Coenzyme Q10 (CoQ10) for renal I/R treatment in animal model. The mitochondria-targeted TPP CoQ10 nanoparticles (T-NPCoQ10) were synthesized through ABC miktoarm polymers method and characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The I/R mouse model and oxygen-glucose deprivation/reperfusion (D/R) model were created to examine the role of T-NPCoQ10 on renal I/R. Mitochondrial DNA damage, apoptosis, and inflammatory cytokines were measured in I/R injury mice. Plasma creatinine, urea nitrogen, tubular injury score was tested to assess the renal function. T-NPCoQ10 nanoparticles could be delivered to renal mitochondria preciously and efficiently. T-NPCoQ10 administration attenuated oxidative injury in both cell and animal models significantly, alleviated mtDNA damage, suppressed inflammatory and apoptotic responses, and improved renal function. The mitochondria specific CoQ10 delivery provided a precious and efficient method for protecting inflammatory and oxidative responses of I/R-induced renal damage.

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.

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.

Enhanced stability, structural characterization and simulated gastrointestinal digestion of coenzyme Q10 loaded ternary nanoparticles

Coenzyme Q10 (CoQ10) is an essential enogenous antioxidant existing in almost all of human somatic cells. However, the self-synthetic ability of CoQ10 is reducing with age until it fails to meet the physiological need. In present study, zein-propylene glycol alginate (PGA)-rhamnolipid (Rha) ternary composite nanoparticles were fabricated using the emulsification-evaporation co-precipitation method for the delivery of CoQ10. The results showed that the addition of rhamnolipid improved the encapsulation efficiency, physicochemical stability and bioaccessibility of CoQ10. Fluorescence spectrum and circular dichroism analyses revealed that the incorporation of CoQ10 and rhamnolipid changed the micro-environment of hydrophobic residues and secondary structure of the protein. Hydrophobic effects, electrostatic interactions and hydrogen bonding were involved in the self-assembly of CoQ10 loaded ternary composite nanoparticles. Differential scanning calorimetry and X-ray diffraction patterns manifested that the nature of CoQ10 encapsulated was amorphous. Atomic force microscope (AFM) and field emission scanning electron microscopy (FE-SEM) demonstrated an spherical shape of composite nanoparticles with a diameter from 82.7 nm to 344.2 nm. Besides, observations of the composite nanoparticles after gastrointestinal tract (GIT) with FE-SEM predicted the potential of ternary composite nanoparticles as a promising vehicle of CoQ10 to be enriched in functional foods.

Coenzyme Q10-Loaded Fish Oil-Based Bigel System: Probing the Delivery Across Porcine Skin and Possible Interaction with Fish Oil Fatty Acids.

Coenzyme Q10 (CoQ10) is a vitamin-like oil-soluble molecule that has anti-oxidant and anti-ageing effects. To determine the most optimal CoQ10 delivery vehicle, CoQ10 was solubilised in both water and fish oil, and formulated into hydrogel, oleogel and bigel. Permeability of CoQ10 from each formulation across porcine ear skin was then evaluated. Furthermore, the effects of the omega-3 fatty eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids from fish oil on skin permeation were investigated by means of nuclear magnetic resonance (NMR) and computerised molecular modelling docking experiments. The highest drug permeation was achieved with the bigel formulation that proved to be the most effective vehicle in delivering CoQ10 across the skin membrane due to a combination of its adhesive, viscous and lipophilic properties. Furthermore, the interactions between CoQ10 and fatty acids revealed by NMR and molecular modelling experiments likely accounted for skin permeability of CoQ10. NMR data showed dose-dependent changes in proton chemical shifts in EPA and DHA. Molecular modelling revealed complex formation and large binding energies between fatty acids and CoQ10. This study advances the knowledge about bigels as drug delivery vehicles and highlights the use of NMR and molecular docking studies for the prediction of the influence of drug-excipient relationships at the molecular level.

NANOEMULSION GEL OF NUTRACEUTICAL CO-ENZYME Q10 AS AN ALTERNATIVE TO CONVENTIONAL TOPICAL DELIVERY SYSTEM TO ENHANCE SKIN PERMEABILITY AND ANTI-WRINKLE EFFICIENCY

Objective: The object of our investigation was to develop and characterize nanoemulsion gel (NEG) as transdermal delivery systems for the poorly water soluble drug, Co-enzyme Q10 (CoQ10), to improve its solubility and skin permeability and thus improving its anti-wrinkle efficiency.Methods: An optimized nanoemulsion (NE) formula was chosen according to its particle size and stability and converted into nanoemulsion gel using different gelling agents, including; carbopol 934 (1%), xanthan gum (2%) and sodium carboxymethyl cellulose(NaCMC) (2%). Drug loaded nanoemulsion gels were characterized for particle size, zeta potential, viscosity and rheological behavior, conductivity, spreadability, drug content and permeation studies using Franz diffusion cell.Results: NEG containing 10% w/v isopropyl myristate (IPM) as oil, 60% w/v tween 80 and transcutol HP as surfactant/co-surfactant mixture (S/CoS), 30%w/v water, 2%w/v drug, and 1% w/v carbopol 934 as gelling gent was concluded as an optimized NEG formula. It exhibited pH, viscosity, drug content, particle size, zeta potential, polydispersity index(PDI) and spreadability, as 5.4±0.011, 27588±2034.34 cps,101.51±0.93%,120.5±1.19 nm,-29.8±1.46, 0.273 and 6.16±0.28 cm, respectively. Also, it showed significantly higher cumulative amount of drug permeated through dialysis membrane (281.71±0.97μg/cm2) and through rat skin (20.73±2.5 μg/cm2) than the other formulae and marketed formulation (P&lt;0.001). In addition, its permeability parameters like drug flux (Jss), enhancement ratio (Er) and permeability coefficient (Kp) exhibited the highest values; 12.79µg/cm2/h, 95.92×10-4 cm2/h and 57.35, respectively for in vitro permeation study and 0.968µg/cm2/h, 7.26×10-4 cm2/h and 1.183, respectively for ex-vivo permeation study.Further histopathological evaluation test showed that CoQ10 NEG has a good anti-wrinkle efficacy compared to the conventional topical dosage form.Conclusion: These results judged NEG to be a promising alternative carrier for topical delivery of CoQ10 to enhance its solubility, skin permeability and thus anti-wrinkle efficiency.

Improved photostability and cytotoxic effect of coenzyme Q10 by its association with vitamin E acetate in polymeric nanocapsules

The present study showed the development of nanocapsules containing the association of the coenzyme Q10 and vitamin E acetate and the evaluation of their effect on in vitro cells culture of malignant glioma and melanoma. In order to investigate if nanocapsules are able to protect coenzyme Q10 from degradation under UVC radiation, a photostability study was carried out. For this, three concentrations of vitamin E acetate were evaluated (1%, 2%, or 3%). Nanocapsules presented suitable physicochemical characteristics and were able to protect coenzyme Q10 from photodegradation. In addition, this protection was influenced by higher vitamin E acetate concentrations, attributing to this oil an important role on coenzyme Q10 photostabilization. Regarding to in vitro citotoxicity assay, nanocapsules containing coenzyme Q10 and 2% vitamin E significantly reduced glioma and melanoma cell viability in 61% and 66%, respectively. In this sense, these formulations represent interesting platforms for the delivery of coenzyme Q10 and vitamin E acetate, presenting effect on the reduction of malignant cells viability.

Mitochondrial delivery of Coenzyme Q10via systemic administration using a MITO-Porter prevents ischemia/reperfusion injury in the mouse liver

We herein report on a mitochondrial therapeutic effect based on the delivery of coenzyme Q10 (CoQ10), an anti-oxidant, to in vivo mitochondria using a MITO-Porter, a liposome-based mitochondrial delivery system that functions via membrane fusion. To evaluate the effects, we used a mouse liver ischemia/reperfusion injury (I/R injury) model, in which mitochondrial reactive oxygen species are overexpressed. We packaged CoQ10 in the lipid phase of a MITO-Porter and optimized the mitochondrial fusogenic activities to produce the CoQ10-MITO-Porter. A histological observation of the carriers in the liver by confocal laser scanning microscopy was done and the accumulation of the carrier labeled with a radio isotope in the liver confirmed that the CoQ10-MITO-Porter was delivered to liver mitochondria via systemic injection. These analytical results permitted us to optimize the compositions of the CoQ10-MITO-Porter so as to permit it to efficiently accumulate in mouse liver mitochondria. Finally, we applied the optimized CoQ10-MITO-Porter to mice via tail vein injection, and hepatic I/R injury was then induced, followed by measuring serum alanine aminotransferase (ALT) levels, a marker of liver injury. We confirmed that the use of the CoQ10-MITO-Porter resulted in a significant decrease in serum ALT levels, indicating that in vivo mitochondrial delivery of the CoQ10via MITO-Porter prevents I/R injury in mice livers. This provides a demonstration of the potential use of such a delivery system in mitochondrial therapies.

Ultra-small NLC for improved dermal delivery of coenyzme Q10

Coenzyme Q10 (CoQ10) acts as an antioxidant in the skin and is frequently contained in anti-aging products. In previous studies, it could be shown that nano-structured lipid carriers (NLC) with a size of about 230 nm are beneficial for the dermal delivery of CoQ10. They increased Q10 skin penetration when compared to equally sized nanoemulsion. In this study, ultra-small NLC were prepared with even smaller mean particles sizes of around 80 nm. The influence of this decrease of particle size was investigated in terms of skin permeation and penetration as well as physicochemical stability of the NLC. Improved dermal delivery of CoQ10 by ultra-small NLC could be achieved.

Design and evaluation of multifunctional nanocarriers for selective delivery of coenzyme Q10 to mitochondria.

Impairments of mitochondrial functions have been associated with failure of cellular functions in different tissues, leading to various pathologies. We report here a mitochondria-targeted nanodelivery system for coenzyme Q10 (CoQ10) that can reach mitochondria and deliver CoQ10 in adequate quantities. Multifunctional nanocarriers based on ABC miktoarm polymers (A = poly(ethylene glycol (PEG), B = polycaprolactone (PCL), and C = triphenylphosphonium bromide (TPPBr)) were synthesized using a combination of click chemistry with ring-opening polymerization, self-assembled into nanosized micelles, and were employed for CoQ10 loading. Drug loading capacity (60 wt %), micelle size (25-60 nm), and stability were determined using a variety of techniques. The micelles had a small critical association concentration and were colloidally stable in solution for more than 3 months. The extraordinarily high CoQ10 loading capacity in the micelles is attributed to good compatibility between CoQ10 and PCL, as indicated by the low Flory-Huggins interaction parameter. Confocal microscopy studies of the fluorescently labeled polymer analog together with the mitochondria-specific vital dye label indicated that the carrier did indeed reach mitochondria. The high CoQ10 loading efficiency allowed testing of micelles within a broad concentration range and provided evidence for CoQ10 effectiveness in two different experimental paradigms: oxidative stress and inflammation. Combined results from chemical, analytical, and biological experiments suggest that the new miktoarm-based carrier provides a suitable means of CoQ10 delivery to mitochondria without loss of drug effectiveness. The versatility of the click chemistry used to prepare this new mitochondria-targeting nanocarrier offers a widely applicable, simple, and easily reproducible procedure to deliver drugs to mitochondria or other intracellular organelles.

The advantages of a novel CoQ10 delivery system in skin photo-protection

Skin photo-ageing induced by ultraviolet (UV) radiation is mainly ascribed to oxidative stress and reactive oxygen species (ROS). Coenzyme Q10 (CoQ10) has been reported as a powerful antioxidant in plasma. However, CoQ10 was barely satisfactory in topical drug delivery because of its lipid solubility. To improve the anti-oxidative efficiency of CoQ10 in skin photo-ageing, the present research prepared a novel CoQ10 nano-structured lipid carrier (CoQ10-NLC) and characterised it by size and freeze-fracture transmission electron microscopy (FF-TEM). In UVA-irradiated fibroblasts, the protection of CoQ10-NLC was more effective than the CoQ10-emulsion as demonstrated by cell viability and morphological changes of the cell body and nucleus. In addition, malondialdehyde (MDA, the product of lipid peroxidation) concentration decreased by 61.5% in the group treated with CoQ10-NLC compared to the group subjected to general CoQ10-emulsion. In the presence of CoQ10-NLC, the activities of the anti-oxidative enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) were reinstated to 81% and 75%, respectively, of the control group. In vivo, the CoQ10-NLC displayed a stronger capability to penetrate the stratum corneum and permeate the dermis after a topical skin application. These results reveal that CoQ10-NLC has greater antioxidant properties and topical skin penetration than the CoQ10-emulsion.

Preparation and characterization of novel coenzyme Q10 nanoparticles engineered from microemulsion precursors.

The purpose of these studies was to prepare and characterize nanoparticles into which Coenzyme Q10 (CoQ10) had been incorporated (CoQ10-NPs) using a simple and potentially scalable method. CoQ10-NPs were prepared by cooling warm microemulsion precursors composed of emulsifying wax, CoQ10, Brij 78, and/or Tween 20. The nanoparticles were lyophilized, and the stability of CoQ10-NPs in both lyophilized form and aqueous suspension was monitored over 7 days. The release of CoQ10 from the nanoparticles was investigated at 37 degrees C. Finally, an in vitro study of the uptake of CoQ10-NPs by mouse macrophage, J774A.1, was completed. The incorporation efficiency of CoQ10 was approximately 74% +/- 5%. Differential Scanning Calorimetry (DSC) showed that the nanoparticle was not a physical mixture of its individual components. The size of the nanoparticles increased over time if stored in aqueous suspension. However, enhanced stability was observed when the nanoparticles were stored at 4 degrees C. Storage in lyophilized form demonstrated the highest stability. The in vitro release profile of CoQ10 from the nanoparticles showed an initial period of rapid release in the first 9 hours followed by a period of slower and extended release. The uptake of CoQ10-NPs by the J774A.1 cells was over 4-fold higher than that of the CoQ10-free nanoparticles (P < .05). In conclusion, CoQ10-NPs with potential application for oral CoQ10 delivery were engineered readily from microemulsion precursors.