Chitosan/Cyclodextrin Nanospheres for Potential Nose-to-Brain Targeting of Idebenone
Idebenone (IDE) is a powerful antioxidant that is potentially active towards cerebral diseases, but its low water solubility and fast first pass metabolism reduce its accumulation in the brain, making it ineffective. In this work, we developed cyclodextrin-based chitosan nanospheres (CS NPs) as pote...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-09-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/10/1206 |
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| author | Federica De Gaetano Nicola d’Avanzo Antonia Mancuso Anna De Gaetano Giuseppe Paladini Francesco Caridi Valentina Venuti Donatella Paolino Cinzia Anna Ventura |
| author_facet | Federica De Gaetano Nicola d’Avanzo Antonia Mancuso Anna De Gaetano Giuseppe Paladini Francesco Caridi Valentina Venuti Donatella Paolino Cinzia Anna Ventura |
| author_sort | Federica De Gaetano |
| collection | DOAJ |
| description | Idebenone (IDE) is a powerful antioxidant that is potentially active towards cerebral diseases, but its low water solubility and fast first pass metabolism reduce its accumulation in the brain, making it ineffective. In this work, we developed cyclodextrin-based chitosan nanospheres (CS NPs) as potential carriers for nose-to-brain targeting of IDE. Sulfobutylether-β-cyclodextrin (SBE-β-CD) was used as a polyanion for chitosan (CS) and as a complexing agent for IDE, permitting its encapsulation into nanospheres (NPs) produced in an aqueous solution. Overloading NPs were obtained by adding the soluble IDE/hydroxypropyl-β-CD (IDE/HP-β-CD) inclusion complex into the CS or SBE-β-CD solutions. We obtained homogeneous CS NPs with a hydrodynamic radius of about 140 nm, positive zeta potential (about +28 mV), and good encapsulation efficiency and drug loading, particularly for overloaded NPs. A biphasic release of IDE, finished within 48 h, was observed from overloaded NPs, whilst non-overloaded CS NPs produced a prolonged release, without a burst effect. In vitro biological studies showed the ability of CS NPs to preserve the antioxidant activity of IDE on U373 culture cells. Furthermore, Fourier transform infrared spectroscopy (FT-IR) demonstrated the ability of CS NPs to interact with the excised bovine nasal mucosa, improving the permeation of the drug and potentially favoring its accumulation in the brain. |
| first_indexed | 2024-03-09T19:36:12Z |
| format | Article |
| id | doaj.art-089ee05bb1354216946af74977989937 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T19:36:12Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-089ee05bb1354216946af749779899372023-11-24T01:51:02ZengMDPI AGPharmaceuticals1424-82472022-09-011510120610.3390/ph15101206Chitosan/Cyclodextrin Nanospheres for Potential Nose-to-Brain Targeting of IdebenoneFederica De Gaetano0Nicola d’Avanzo1Antonia Mancuso2Anna De Gaetano3Giuseppe Paladini4Francesco Caridi5Valentina Venuti6Donatella Paolino7Cinzia Anna Ventura8Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres 31, I-98166 Messina, ItalyDepartment of Pharmacy, University “G. D’annunzio” of Chieti-Pescara, Via dei Vestini, 31, I-66100 Chieti, ItalyDepartment of Experimental and Clinical Medicine, University of Catanzaro “Magna Graecia”, Viale Europa s.n.c., I-88100 Catanzaro, ItalyDepartment of Life Sciences, University of Modena, Via Dei Campi, 287, 41125 Modena, ItalyDepartment of Mathematical and Computer Sciences, Physical Sciences and Earth Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres 31, I-98166 Messina, ItalyDepartment of Mathematical and Computer Sciences, Physical Sciences and Earth Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres 31, I-98166 Messina, ItalyDepartment of Mathematical and Computer Sciences, Physical Sciences and Earth Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres 31, I-98166 Messina, ItalyDepartment of Experimental and Clinical Medicine, University of Catanzaro “Magna Graecia”, Viale Europa s.n.c., I-88100 Catanzaro, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres 31, I-98166 Messina, ItalyIdebenone (IDE) is a powerful antioxidant that is potentially active towards cerebral diseases, but its low water solubility and fast first pass metabolism reduce its accumulation in the brain, making it ineffective. In this work, we developed cyclodextrin-based chitosan nanospheres (CS NPs) as potential carriers for nose-to-brain targeting of IDE. Sulfobutylether-β-cyclodextrin (SBE-β-CD) was used as a polyanion for chitosan (CS) and as a complexing agent for IDE, permitting its encapsulation into nanospheres (NPs) produced in an aqueous solution. Overloading NPs were obtained by adding the soluble IDE/hydroxypropyl-β-CD (IDE/HP-β-CD) inclusion complex into the CS or SBE-β-CD solutions. We obtained homogeneous CS NPs with a hydrodynamic radius of about 140 nm, positive zeta potential (about +28 mV), and good encapsulation efficiency and drug loading, particularly for overloaded NPs. A biphasic release of IDE, finished within 48 h, was observed from overloaded NPs, whilst non-overloaded CS NPs produced a prolonged release, without a burst effect. In vitro biological studies showed the ability of CS NPs to preserve the antioxidant activity of IDE on U373 culture cells. Furthermore, Fourier transform infrared spectroscopy (FT-IR) demonstrated the ability of CS NPs to interact with the excised bovine nasal mucosa, improving the permeation of the drug and potentially favoring its accumulation in the brain.https://www.mdpi.com/1424-8247/15/10/1206idebenonechitosan nanospherescyclodextrinsin vitro biological studiesFT-IR |
| spellingShingle | Federica De Gaetano Nicola d’Avanzo Antonia Mancuso Anna De Gaetano Giuseppe Paladini Francesco Caridi Valentina Venuti Donatella Paolino Cinzia Anna Ventura Chitosan/Cyclodextrin Nanospheres for Potential Nose-to-Brain Targeting of Idebenone Pharmaceuticals idebenone chitosan nanospheres cyclodextrins in vitro biological studies FT-IR |
| title | Chitosan/Cyclodextrin Nanospheres for Potential Nose-to-Brain Targeting of Idebenone |
| title_full | Chitosan/Cyclodextrin Nanospheres for Potential Nose-to-Brain Targeting of Idebenone |
| title_fullStr | Chitosan/Cyclodextrin Nanospheres for Potential Nose-to-Brain Targeting of Idebenone |
| title_full_unstemmed | Chitosan/Cyclodextrin Nanospheres for Potential Nose-to-Brain Targeting of Idebenone |
| title_short | Chitosan/Cyclodextrin Nanospheres for Potential Nose-to-Brain Targeting of Idebenone |
| title_sort | chitosan cyclodextrin nanospheres for potential nose to brain targeting of idebenone |
| topic | idebenone chitosan nanospheres cyclodextrins in vitro biological studies FT-IR |
| url | https://www.mdpi.com/1424-8247/15/10/1206 |
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