At the highest concentration used (50 microM), a toxic effect of the free and liposomally entrapped drug was observed. To evaluate the effects on astrocytes, three different drug concentrations were used (0.5 microM, 5 microM, and 50 microM). The following parameters were taken into consideration to assay free or liposomally entrapped idebenone: lactic dehydrogenase release, respiratory capacity measured by tetrazolium salt conversion, glutamine synthetase, and the levels of constitutive and inducible 70-kDa heat shock proteins. In particular, both the concentration-dependent effects and the therapeutic effectiveness toward excitotoxic injury, elicited by chronic treatment with ethanol (100 microM) for 12 days, were evaluated. The potential therapeutic advantages of the encapsulation of idebenone within pegylated liposomes were investigated in vitro on primary cortical astrocytes of rats. The results of these studies will be illustrated with emphasis on the most innovative strategies and their future perspectives. 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. In recent decades, many strategies have been proposed to improve IDE effectiveness in the treatment of neurodegenerative diseases and skin disorders. 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. One of the most potent antioxidants available for pharmaceutical and cosmetic use is Idebenone (IDE), a synthetic analogue of Coenzyme Q10. The key role of antioxidants in treating and preventing many systemic and topical diseases is well recognized.
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