Idebenone (IDE) has been proposed for the treatment of
neurodegenerative diseases involving
mitochondria dysfunctions. Unfortunately, to date, IDE therapeutic treatments have not been as successful as expected. To improve IDE efficacy, in this work we describe a two-step approach: (1) synthesis of IDE
ester derivatives by covalent linking IDE to other two
antioxidants,
trolox (IDETRL) and
lipoic acid (IDELIP), to obtain a synergic effect; (2) loading of IDE, IDETRL, or IDELIP into solid
lipid nanoparticles (SLN) to improve IDE and its
esters' water solubility while increasing and prolonging their
antioxidant activity. IDE and its derivatives loaded SLN showed good physico-chemical and technological properties (spherical shape, mean particle sizes 23-25 nm, single peak in the size distribution, ζ potential values -1.76/-2.89 mV, and good stability at room temperature). In vitro
antioxidant activity of these SLN was evaluated in comparison with free drugs by means of
oxygen radical absorbance capacity (ORAC) test. IDETRL and IDELIP showed a greater
antioxidant activity than IDE and encapsulation of IDE and its derivatives into SLN was able to prolong their
antioxidant activity. These results suggest that loading IDETRL and IDELIP into SLN could be a useful strategy to improve IDE efficacy.