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

Biomolecules - Tập 9 Số 10 - Trang 531
Valentina Venuti1, Vincenza Crupi2, Barbara Fazio3, D. Majolino4, Giuseppe Acri5, Barbara Testagrossa5, Rosanna Stancanelli2, Federica De Gaetano2, Agnese Gagliardi6, Donatella Paolino6, Giuseppe Floresta7, Venerando Pistarà7, Antonio Rescifina7, Cinzia Anna Ventura2
1Dipartimento di Scienze Matematiche e Informatiche, Scienze Fisiche e Scienze della Terra, Università degli Studi di Messina, V.le F. Stagno D'Alcontres, 31-98166 Messina, Italy. [email protected].
2Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche e Ambientali, Università degli Studi di Messina, V.le F. Stagno D’Alcontrés, 31-98166 Messina, Italy
3CNR-IPCF Istituto per i Processi Chimico Fisici, V.le F. Stagno d’Alcontres, 37-98158 Faro Superiore, Messina, Italy
4Dipartimento di Scienze Matematiche e Informatiche, Scienze Fisiche e Scienze della Terra, Università degli Studi di Messina, V.le F. Stagno D’Alcontres, 31-98166 Messina, Italy
5Dipartimento di Scienze Biomediche, Odontoiatriche, e delle Immagini Morfologiche e Funzionali, Università degli Studi di Messina, c/o A.O.U. Policlinico “G. Martino” Via Consolare Valeria, 1-98125 Messina, Italy
6Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Catanzaro “Magna Græcia”, Campus Universitario “S. Venuta”, Viale S. Venuta-88100 Germaneto, Catanzaro, Italy
7Dipartimento di Scienze del Farmaco, Università degli Studi di Catania, V.le A. Doria, 6-95125 Catania, Italy

Tóm tắt

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.

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