# Assessment of the Technological Properties of Idebenone and
###### Abstract  
Several liquid lipids have been proposed to obtain nanostructured lipid carriers (NLC) with improved efficiency. An attractive strategy is the use of oils that could elicit a synergic effect with the loaded drug. In this work, different percentages (0-4% \(w/w\)) of tocophenyl acetate (TA), an oily antioxidant, were used as liquid lipid to prepare NLC loading idebenone (IDE), a synthetic antioxidant investigated for the treatment of neurodegenerative and topical diseases. The technological properties of such NLC were evaluated, as well as the interactions among lipid core components. Loading different percentages of IDE (1-4% \(w/w\)) into NLC containing TA up to 4% \(w/w\), no significant change of mean size and polydispersity index was observed. IDE loading capacity was 4% \(w/w\) but NLC containing IDE percentages greater than 1.5% \(w/w\) showed poor stability during long-term storage. Differential scanning calorimetry analyses highlighted linear relationships between peak temperature and TA percentages, while the enthalpy variation and recrystallization index values showed that increasing the percentage of TA led to less crystalline structure of the NLC core. Therefore, NLC co-loading IDE and TA could be useful to design new delivery systems for the treatment of diseases that could benefit from the co-administration of these antioxidants. debene; tocophenyl acetate; lipid nanoparticles; differential scanning calorimetry +
Footnote †: journal: Applied Sciences  
19 March 2021  
12 April 2021  
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**1. Introduction**  
In the last decades, lipid nanoparticles have gained a great deal of attention in the pharmaceutical field owing to their advantages as drug delivery systems [1; 2; 3; 4; 5]. In the 1990s, the first generation of lipid nanoparticles, namely solid lipid nanoparticles (SLN), was developed and investigated as carriers for the delivery of a great variety of active ingredients by different administration routes [6; 7; 8; 9; 10]. SLN consist of a solid lipid core stabilized by different types of surfactants in aqueous media. SLN drawbacks, such as poor loading capacity and drug leakage from the nanoparticles during storage, prompted the researchers to design a second generation of lipid nanoparticles, named nanostructured lipid carriers (NLC). The amorphous structure and/or the presence of liquid lipids as oily compartments of the lipid core made these nanoparticles able to accommodate a greater amount of drug compared to SLN, while preventing drug expulsion from the nano-carriers during storage [11; 12]. Various solid and liquid lipids have been assessed as components of the NLC core in the attempt to improve the potential therapeutic efficiency of such delivery systems [13]. A promising strategy that could provide NLC with better therapeutic outcomes is the use of liquid lipids with an inherent biological activity that could elicit a synergic effect with the loaded drug. In a previous paper [14], idebenone (IDE), a potent synthetic antioxidant analogous of coenzyme Q\({}_{10}\)[15; 16], was loaded into NLCwhose lipid components were cetyl palmit, a solid wax of GRAS (Generally Regarded As Safe) status, and tocopheryl acetate (TA), a lipophilic liquid that is regarded as a potent antioxidant in the human body [17, 18]. After topical treatment of human volunteers with a gel containing NLC co-loading IDE and TA, an increased photo-protective activity was observed compared to IDE-loaded SLN incorporated in the same vehicle. However, in the abovementioned study, the effects of co-loading different percentages of IDE and TA on the technological properties of the resulting NLC were not investigated.