Strategies for oral delivery and mitochondrial targeting of CoQ10

Abstract

Coenzyme Q10 (CoQ10), also known as ubiquinone or ubidecarenone, is a powerful, endogenously produced, intracellularly existing lipophilic antioxidant. It combats reactive oxygen species (ROS) known to be responsible for a variety of human pathological conditions. Its target site is the inner mitochondrial membrane (IMM) of each cell. In case of deficiency and/or aging, CoQ10 oral supplementation is warranted. However, CoQ10 has low oral bioavailability due to its lipophilic nature, large molecular weight, regional differences in its gastrointestinal permeability and involvement of multitransporters. Intracellular delivery and mitochondrial target ability issues pose additional hurdles. To maximize CoQ10 delivery to its biopharmaceutical target, numerous approaches have been undertaken. The review summaries the current research on CoQ10 bioavailability and highlights the headways to obtain a satisfactory intracellular and targeted mitochondrial delivery. Unresolved questions and research gaps were identified to bring this promising natural product to the forefront of therapeutic agents for treatment of different pathologies.

Clinical syndromes associated with Coenzyme Q10 deficiency

“…Barriers for tissues CoQ delivery have been found due to its high molecular weight and poor aqueous solubility, but at high doses, dietary supplementation increases CoQ levels in all tissues, including heart and brain, especially with certain formulations (132,133). Remarkably, the effectivity of 2,4-dHB depends on the nature of the COQ7 mutation and the residual activity of the protein (102).…”

Vitamin C and ubiquinone have the same ability in reducing the spermatozoa DNA fragmentation index in infertile men at Doctor Soetomo General Hospital, Surabaya, Indonesia

“…The low oral bioavailability of Ubiquinone is caused by a considerable molecular weight, high lipophilicity, poor solubility in water, regional variations in Ubiquinone permeability in the gastrointestinal tract, and multi transporter involvement. 23 Many studies are currently developing approaches to address these issues, such as the use of solid or dry emulsion formulations, nanoliposomes, nanoparticles with biodegradable surfactant/stabilizer capable of reducing plasma lipid peroxide levels, membrane-penetrating lipophilic cations, and mitochondrial-targeted nano-systems that are effective against oxidative and inflammatory stress. 23 Our data did not show any significant improvement of spermatozoa DNA fragmentation after in vivo Vitamin C and Ubiquinone combination for 35 days.…”

“…23 Many studies are currently developing approaches to address these issues, such as the use of solid or dry emulsion formulations, nanoliposomes, nanoparticles with biodegradable surfactant/stabilizer capable of reducing plasma lipid peroxide levels, membrane-penetrating lipophilic cations, and mitochondrial-targeted nano-systems that are effective against oxidative and inflammatory stress. 23 Our data did not show any significant improvement of spermatozoa DNA fragmentation after in vivo Vitamin C and Ubiquinone combination for 35 days. Previous studies that have existed so far used a combination of several types of antioxidants.…”

Redefining infantile-onset multisystem phenotypes of coenzyme Q10-deficiency in the next-generation sequencing era

“…We cannot compare the effects of different dosages because formulations and durations of treatment also varied [10] . We recommend high doses of CoQ 10 supplementation (> 30 mg/kg), because inadequate dosage and duration of intake have often constrained uptake of exogenous CoQ 10 [59][60][61] , with few mild reported side effects [10] .…”