In Vitro Antioxidant Activity of Idebenone Derivative-Loaded Solid Lipid Nanoparticles

Abstract

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.

In Vitro Antioxidant Activity and In Vivo Topical Efficacy of Lipid Nanoparticles Co-Loading Idebenone and Tocopheryl Acetate

“…In addition, we did not observe any sign of drug precipitation during storage. Similar low ζ-potential vales were obtained in previous works on SLN with the same composition, and their good stability was attributed to their high PIT values [17,20,30].…”

“…Therefore, we reported as an example in Figure 1 TEM pictures of only SLN IDE1 and NLC IDE1. IDE loading into SLN and NLC was determined as the maximum amount of drug that could be incorporated in the carriers leading to a clear colloidal system, as previously reported [17,20,30]. IDE loading into SLN and NLC was 1.5 and 2%, respectively.…”

Idebenone: Novel Strategies to Improve Its Systemic and Local Efficacy

“…A very recent study [ 90 ] described a two-step approach aimed at improving IDE efficacy increasing its water solubility and its antioxidant activity. First, the authors synthesized IDE ester derivatives by covalent linking IDE to other two antioxidants, trolox (IDETRL) and lipoic acid (IDELIP) to obtain a synergic effect and then, they loaded these IDE derivatives into SLNs.…”

Solid Lipid Nanoparticles Loading Idebenone Ester with Pyroglutamic Acid: In Vitro Antioxidant Activity and In Vivo Topical Efficacy

“…In the last decade, a great deal of attention has been focused on SLN utilized as carriers for dermal delivery of antioxidants because of their ability to protect these molecules from degradation and to improve their topical bioavailability [5,6,7,8,9]. In a previous work, we reported a prolonged in vitro antioxidant activity upon loading idebenone (IDE) and IDE derivatives into SLN [10]. IDE is a synthetic analogue of CoQ 10 , which has been proposed both for the treatment of neurodegenerative diseases [11,12,13] and for topical use in the therapy of several skin disorders [14].…”

“…At present, the development of bifunctional molecules is regarded as a promising approach to improve the therapeutic outcome in comparison to a two-drug administration, reducing drug dosage and side effects [27,28]. Previously, to improve IDE effectiveness, we reported a two-step approach consisting of synthesizing ester derivatives by covalent linking IDE to other two antioxidants and subsequent loading of these molecules into SLN [10]. This strategy provided that IDE derivatives showed increased and prolonged antioxidant activity upon loading into SLN.…”