Physicochemical Characterization and Antioxidant Activity Evaluation of Idebenone/Hydroxypropyl-β-Cyclodextrin Inclusion Complex †.

Valentina Venuti,Vincenza Crupi,Antonio Rescifina,Federica De Gaetano,Agnese Gagliardi,Giuseppe Acri,Barbara Fazio,Cinzia A Ventura,Venerando Pistarà,Barbara Testagrossa,Donatella Paolino,Domenico Majolino,Rosanna Stancanelli,Giuseppe Floresta

doi:10.3390/biom9100531

Abstract

Idebenone (IDE) is an antioxidant drug active at the level of the central nervous system (CNS), whose poor water solubility limits its clinical application. An IDE/2-hydroxypropyl-β-cyclodextrin (IDE/HP-β-CD) inclusion complex was investigated by combining experimental methods and theoretical approaches. Furthermore, biological in vitro/ex vivo assays were performed. Phase solubility studies showed an AL type diagram, suggesting the presence of a 1:1 complex with high solubility. Scanning electron microscopy (SEM) allowed us to detect the morphological changes upon complexation. The intermolecular interactions stabilizing the inclusion complex were experimentally characterized by exploring the complementarity of Fourier-transform infrared spectroscopy in attenuated total reflectance geometry (FTIR-ATR) with mid-infrared light, Fourier-transform near-infrared (FT-NIR) spectroscopy, and Raman spectroscopy. From the temperature evolution of the O–H stretching band of the complex, the average enthalpy ΔHHB of the hydrogen bond scheme upon inclusion was obtained. Two-dimensional (2D) rotating frame Overhauser effect spectroscopy (ROESY) analysis and computational studies involving molecular modeling and molecular dynamics (MD) simulation demonstrated the inclusion of the quinone ring of IDE inside the CD ring. In vitro/ex vivo studies evidenced that complexation produces a protective effect of IDE against the H2O2-induced damage on human glioblastoma astrocytoma (U373) cells and increases IDE permeation through the excised bovine nasal mucosa.

Highlights

Idebenone (2,3-dimethoxy-5-methyl-6-(10-idroxydecyl)-1,4-benzoquinone;(2,3-dimethoxy-5-methyl-6-(10-idroxydecyl)-1,4-benzoquinone;IDE, IDE, Figure 1) an is1) is an analog of coenzyme Q10(CoQ10), a vital cell membrane antioxidant and an essential part analog of coenzyme Q10 (CoQ10), a vital cell membrane antioxidant and an essential part of the of the cellular machinery used toadenosine produce triphosphate adenosine triphosphate [1]. antioxidantIt is a potent cellular machinery used to produce (ATP) [1]
Dosage forms different from tablets may be needed
1 and ω2, system, we considered a first class H-bonded) of non-H-bonded

Summary

Introduction

Idebenone (2,3-dimethoxy-5-methyl-6-(10-idroxydecyl)-1,4-benzoquinone;(2,3-dimethoxy-5-methyl-6-(10-idroxydecyl)-1,4-benzoquinone;IDE, IDE, Figure 1) an is1) is an analog of coenzyme Q10(CoQ10), a vital cell membrane antioxidant and an essential part analog of coenzyme Q10 (CoQ10), a vital cell membrane antioxidant and an essential part of the of the cellular machinery used toadenosine produce triphosphate adenosine triphosphate [1]. antioxidantIt is a potent cellular machinery used to produce (ATP) [1]. (CoQ10), a vital cell membrane antioxidant and an essential part analog of coenzyme Q10 (CoQ10), a vital cell membrane antioxidant and an essential part of the of the cellular machinery used toadenosine produce triphosphate adenosine triphosphate [1]. It is a potent cellular machinery used to produce (ATP) [1]. Is a potent able antioxidant able to retard lipid peroxidation, thereby protectingagainst mitochondria against oxidative stress. To retard lipid peroxidation, thereby protecting mitochondria oxidative stress.

Methods

Results

Discussion

Conclusion