Physicochemical Characterization and Antioxidant Activity Evaluation of Idebenone/Hydroxypropyl-<i>β</i>-Cyclodextrin Inclusion Complex <xref rid="fn1-biomolecules-570665" ref-type="fn">†</xref>
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-<i>β</i>-cyclodextrin (IDE/HP-<i>β</i>-CD) inclusion complex was investigated...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2019-09-01
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| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/9/10/531 |
| _version_ | 1828166263499653120 |
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| author | Valentina Venuti Vincenza Crupi Barbara Fazio Domenico Majolino Giuseppe Acri Barbara Testagrossa Rosanna Stancanelli Federica De Gaetano Agnese Gagliardi Donatella Paolino Giuseppe Floresta Venerando Pistarà Antonio Rescifina Cinzia A. Ventura |
| author_facet | Valentina Venuti Vincenza Crupi Barbara Fazio Domenico Majolino Giuseppe Acri Barbara Testagrossa Rosanna Stancanelli Federica De Gaetano Agnese Gagliardi Donatella Paolino Giuseppe Floresta Venerando Pistarà Antonio Rescifina Cinzia A. Ventura |
| author_sort | Valentina Venuti |
| collection | DOAJ |
| description | 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-<i>β</i>-cyclodextrin (IDE/HP-<i>β</i>-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 A<sub>L</sub> 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 Δ<i>H</i><sub>HB</sub> 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 H<sub>2</sub>O<sub>2</sub>-induced damage on human glioblastoma astrocytoma (U373) cells and increases IDE permeation through the excised bovine nasal mucosa. |
| first_indexed | 2024-04-12T01:58:51Z |
| format | Article |
| id | doaj.art-25bc35aa612a41b6a5c628bc7a6178e3 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-04-12T01:58:51Z |
| publishDate | 2019-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-25bc35aa612a41b6a5c628bc7a6178e32022-12-22T03:52:43ZengMDPI AGBiomolecules2218-273X2019-09-0191053110.3390/biom9100531biom9100531Physicochemical Characterization and Antioxidant Activity Evaluation of Idebenone/Hydroxypropyl-<i>β</i>-Cyclodextrin Inclusion Complex <xref rid="fn1-biomolecules-570665" ref-type="fn">†</xref>Valentina Venuti0Vincenza Crupi1Barbara Fazio2Domenico Majolino3Giuseppe Acri4Barbara Testagrossa5Rosanna Stancanelli6Federica De Gaetano7Agnese Gagliardi8Donatella Paolino9Giuseppe Floresta10Venerando Pistarà11Antonio Rescifina12Cinzia A. Ventura13Dipartimento 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, ItalyDipartimento di Scienze Chimiche, Biologiche, Farmaceutiche e Ambientali, Università degli Studi di Messina, V.le F. Stagno D’Alcontrés, 31-98166 Messina, ItalyCNR-IPCF Istituto per i Processi Chimico Fisici, V.le F. Stagno d’Alcontres, 37-98158 Faro Superiore, Messina, ItalyDipartimento 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, ItalyDipartimento 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, ItalyDipartimento 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, ItalyDipartimento di Scienze Chimiche, Biologiche, Farmaceutiche e Ambientali, Università degli Studi di Messina, V.le F. Stagno D’Alcontrés, 31-98166 Messina, ItalyDipartimento di Scienze Chimiche, Biologiche, Farmaceutiche e Ambientali, Università degli Studi di Messina, V.le F. Stagno D’Alcontrés, 31-98166 Messina, ItalyDipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Catanzaro “Magna Græcia”, Campus Universitario “S. Venuta”, Viale S. Venuta-88100 Germaneto, Catanzaro, ItalyDipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Catanzaro “Magna Græcia”, Campus Universitario “S. Venuta”, Viale S. Venuta-88100 Germaneto, Catanzaro, ItalyDipartimento di Scienze del Farmaco, Università degli Studi di Catania, V.le A. Doria, 6-95125 Catania, ItalyDipartimento di Scienze del Farmaco, Università degli Studi di Catania, V.le A. Doria, 6-95125 Catania, ItalyDipartimento di Scienze del Farmaco, Università degli Studi di Catania, V.le A. Doria, 6-95125 Catania, ItalyDipartimento di Scienze Chimiche, Biologiche, Farmaceutiche e Ambientali, Università degli Studi di Messina, V.le F. Stagno D’Alcontrés, 31-98166 Messina, ItalyIdebenone (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-<i>β</i>-cyclodextrin (IDE/HP-<i>β</i>-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 A<sub>L</sub> 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 Δ<i>H</i><sub>HB</sub> 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 H<sub>2</sub>O<sub>2</sub>-induced damage on human glioblastoma astrocytoma (U373) cells and increases IDE permeation through the excised bovine nasal mucosa.https://www.mdpi.com/2218-273X/9/10/531idebenone(2-hydroxypropyl)-<i>β</i>-cyclodextrininclusion complexphysicochemical characterizationantioxidant activityu373 cellsexcised bovine nasal mucosa |
| spellingShingle | Valentina Venuti Vincenza Crupi Barbara Fazio Domenico Majolino Giuseppe Acri Barbara Testagrossa Rosanna Stancanelli Federica De Gaetano Agnese Gagliardi Donatella Paolino Giuseppe Floresta Venerando Pistarà Antonio Rescifina Cinzia A. Ventura Physicochemical Characterization and Antioxidant Activity Evaluation of Idebenone/Hydroxypropyl-<i>β</i>-Cyclodextrin Inclusion Complex <xref rid="fn1-biomolecules-570665" ref-type="fn">†</xref> Biomolecules idebenone (2-hydroxypropyl)-<i>β</i>-cyclodextrin inclusion complex physicochemical characterization antioxidant activity u373 cells excised bovine nasal mucosa |
| title | Physicochemical Characterization and Antioxidant Activity Evaluation of Idebenone/Hydroxypropyl-<i>β</i>-Cyclodextrin Inclusion Complex <xref rid="fn1-biomolecules-570665" ref-type="fn">†</xref> |
| title_full | Physicochemical Characterization and Antioxidant Activity Evaluation of Idebenone/Hydroxypropyl-<i>β</i>-Cyclodextrin Inclusion Complex <xref rid="fn1-biomolecules-570665" ref-type="fn">†</xref> |
| title_fullStr | Physicochemical Characterization and Antioxidant Activity Evaluation of Idebenone/Hydroxypropyl-<i>β</i>-Cyclodextrin Inclusion Complex <xref rid="fn1-biomolecules-570665" ref-type="fn">†</xref> |
| title_full_unstemmed | Physicochemical Characterization and Antioxidant Activity Evaluation of Idebenone/Hydroxypropyl-<i>β</i>-Cyclodextrin Inclusion Complex <xref rid="fn1-biomolecules-570665" ref-type="fn">†</xref> |
| title_short | Physicochemical Characterization and Antioxidant Activity Evaluation of Idebenone/Hydroxypropyl-<i>β</i>-Cyclodextrin Inclusion Complex <xref rid="fn1-biomolecules-570665" ref-type="fn">†</xref> |
| title_sort | physicochemical characterization and antioxidant activity evaluation of idebenone hydroxypropyl i β i cyclodextrin inclusion complex xref rid fn1 biomolecules 570665 ref type fn † xref |
| topic | idebenone (2-hydroxypropyl)-<i>β</i>-cyclodextrin inclusion complex physicochemical characterization antioxidant activity u373 cells excised bovine nasal mucosa |
| url | https://www.mdpi.com/2218-273X/9/10/531 |
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