Idebenone: Novel Strategies to Improve Its Systemic and Local Efficacy

Abstract

The key role of antioxidants in treating and preventing many systemic and topical diseases is well recognized. One of the most potent antioxidants available for pharmaceutical and cosmetic use is Idebenone (IDE), a synthetic analogue of Coenzyme Q10. Unfortunately, IDE’s unfavorable physicochemical properties such as poor water solubility and high lipophilicity impair its bioavailability after oral and topical administration and prevent its parenteral use. In recent decades, many strategies have been proposed to improve IDE effectiveness in the treatment of neurodegenerative diseases and skin disorders. After a brief description of IDE potential therapeutic applications and its pharmacokinetic and pharmacodynamic profile, this review will focus on the different approaches investigated to overcome IDE drawbacks, such as IDE incorporation into different types of delivery systems (liposomes, cyclodextrins, microemulsions, self-micro-emulsifying drug delivery systems, lipid-based nanoparticles, polymeric nanoparticles) and IDE chemical modification. The results of these studies will be illustrated with emphasis on the most innovative strategies and their future perspectives.

Hyperphosphorylated tau aggregation and cytotoxicity modulators screen identified prescription drugs linked to Alzheimer's disease and cognitive functions

“…Hexachlorophene showed inconsistent results in cell protection assays, due likely to its high propensity to oxidation (data not shown). Idebenone is a coenzyme Q analogue with limited bioavailability 66 . Prednicarbate, a PTAE, appeared to enhance the cell killing by p-tau, while carmofur exhibited borderline effects (Supplemental Fig.…”

“…The likelihood of developing effective therapeutics from these two compounds is therefore higher. In contrast, idebenone, being a potent antioxidant and high lipophilicity, has very low bioavailability 66 . Lastly, both R-(−)apomorphine and raloxifene have been linked to the preservation of cognition 67,68 (detailed in "Discussion" below), suggesting that these prior observations might be related to the control of NFT in the brain.…”

The NRF2 Signaling Network Defines Clinical Biomarkers and Therapeutic Opportunity in Friedreich’s Ataxia

“…Although coenzyme Q 10 , vitamin E and idebenone poorly cross the blood-brain barrier [115][116][117], these compounds have been widely tested in FA clinical trials. The co-administration of coenzyme Q 10 and vitamin E was tested in several small trials, demonstrating a general improvement in cardiac and skeletal muscle bioenergetics, although the neurologic outcome was unaffected [118][119][120].…”

The role of mitochondrial dysfunction in Alzheimer’s disease

“…Эти данные подтверждают ранее опубликованные данные об эффективности идебенона в сохранении функции мышц выдоха в этой популяции пациентов. Стабилизация функции дыхательных мышц может потенциально отсрочить возникновение дыхательной недостаточности у этих пациентов [46]. Необходимы более продолжительные исследования, чтобы дополнительно подтвердить обнадеживающие эффекты лечения идебеноном, как это наблюдалось в рандомизированном контролируемом исследовании DELOS.…”