Oxidized Alginate Dopamine Conjugate: In Vitro Characterization for Nose-to-Brain Delivery Application
Background: The blood–brain barrier (BBB) bypass of dopamine (DA) is still a challenge for supplying it to the neurons of <i>Substantia Nigra</i> mainly affected by Parkinson disease. DA prodrugs have been studied to cross the BBB, overcoming the limitations of DA hydrophilicity. Therefo...
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MDPI AG
2021-06-01
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| Online Access: | https://www.mdpi.com/1996-1944/14/13/3495 |
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| author | Adriana Trapani Filomena Corbo Gennaro Agrimi Nicoletta Ditaranto Nicola Cioffi Filippo Perna Andrea Quivelli Erika Stefàno Paola Lunetti Antonella Muscella Santo Marsigliante Antonio Cricenti Marco Luce Cristina Mormile Antonino Cataldo Stefano Bellucci |
| author_facet | Adriana Trapani Filomena Corbo Gennaro Agrimi Nicoletta Ditaranto Nicola Cioffi Filippo Perna Andrea Quivelli Erika Stefàno Paola Lunetti Antonella Muscella Santo Marsigliante Antonio Cricenti Marco Luce Cristina Mormile Antonino Cataldo Stefano Bellucci |
| author_sort | Adriana Trapani |
| collection | DOAJ |
| description | Background: The blood–brain barrier (BBB) bypass of dopamine (DA) is still a challenge for supplying it to the neurons of <i>Substantia Nigra</i> mainly affected by Parkinson disease. DA prodrugs have been studied to cross the BBB, overcoming the limitations of DA hydrophilicity. Therefore, the aim of this work is the synthesis and preliminary characterization of an oxidized alginate-dopamine (AlgOX-DA) conjugate conceived for DA nose-to-brain delivery. Methods: A Schiff base was designed to connect oxidized polymeric backbone to DA and both AlgOX and AlgOX-DA were characterized in terms of Raman, XPS, FT-IR, and <sup>1</sup>H- NMR spectroscopies, as well as in vitro mucoadhesive and release tests. Results: Data demonstrated that AlgOX-DA was the most mucoadhesive material among the tested ones and it released the neurotransmitter in simulated nasal fluid and in low amounts in phosphate buffer saline. Results also demonstrated the capability of scanning near-field optical microscopy to study the structural and fluorescence properties of AlgOX, fluorescently labeled with fluorescein isothiocyanate microstructures. Interestingly, in SH-SY5Y neuroblastoma cell line up to 100 μg/mL, no toxic effect was derived from AlgOX and AlgOX-DA in 24 h. Conclusions: Overall, the in vitro performances of AlgOX and AlgOX-DA conjugates seem to encourage further ex vivo and in vivo studies in view of nose-to-brain administration. |
| first_indexed | 2024-03-10T10:09:15Z |
| format | Article |
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| issn | 1996-1944 |
| language | English |
| last_indexed | 2024-03-10T10:09:15Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Materials |
| spelling | doaj.art-eb6988f2c9864650a429cd743e65631f2023-11-22T01:22:37ZengMDPI AGMaterials1996-19442021-06-011413349510.3390/ma14133495Oxidized Alginate Dopamine Conjugate: In Vitro Characterization for Nose-to-Brain Delivery ApplicationAdriana Trapani0Filomena Corbo1Gennaro Agrimi2Nicoletta Ditaranto3Nicola Cioffi4Filippo Perna5Andrea Quivelli6Erika Stefàno7Paola Lunetti8Antonella Muscella9Santo Marsigliante10Antonio Cricenti11Marco Luce12Cristina Mormile13Antonino Cataldo14Stefano Bellucci15Department of Pharmacy-Drug Sciences, University of Bari “Aldo Moro”, I-70125 Bari, ItalyDepartment of Pharmacy-Drug Sciences, University of Bari “Aldo Moro”, I-70125 Bari, ItalyDepartment of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari “Aldo Moro”, I-70125 Bari, ItalyDipartimento di Chimica and CSGI-Bari Unit, Università degli Studi di Bari Aldo Moro, I-70125 Bari, ItalyDipartimento di Chimica and CSGI-Bari Unit, Università degli Studi di Bari Aldo Moro, I-70125 Bari, ItalyDepartment of Pharmacy-Drug Sciences, University of Bari “Aldo Moro”, I-70125 Bari, ItalyDepartment of Pharmacy-Drug Sciences, University of Bari “Aldo Moro”, I-70125 Bari, ItalyDipartimento Scienze e Tecnologie Biologiche e Ambientali, University of Salento, I-73100 Lecce, ItalyDipartimento Scienze e Tecnologie Biologiche e Ambientali, University of Salento, I-73100 Lecce, ItalyDipartimento Scienze e Tecnologie Biologiche e Ambientali, University of Salento, I-73100 Lecce, ItalyDipartimento Scienze e Tecnologie Biologiche e Ambientali, University of Salento, I-73100 Lecce, ItalyISM-CNR, Via del Fosso del Cavaliere 100, I-00133 Rome, ItalyISM-CNR, Via del Fosso del Cavaliere 100, I-00133 Rome, ItalyIstituto Nazionale di Fisica Nucleare-Laboratori Nazionali di Frascati, Via Enrico Fermi 54, Frascati, I-00044 Rome, ItalyIstituto Nazionale di Fisica Nucleare-Laboratori Nazionali di Frascati, Via Enrico Fermi 54, Frascati, I-00044 Rome, ItalyIstituto Nazionale di Fisica Nucleare-Laboratori Nazionali di Frascati, Via Enrico Fermi 54, Frascati, I-00044 Rome, ItalyBackground: The blood–brain barrier (BBB) bypass of dopamine (DA) is still a challenge for supplying it to the neurons of <i>Substantia Nigra</i> mainly affected by Parkinson disease. DA prodrugs have been studied to cross the BBB, overcoming the limitations of DA hydrophilicity. Therefore, the aim of this work is the synthesis and preliminary characterization of an oxidized alginate-dopamine (AlgOX-DA) conjugate conceived for DA nose-to-brain delivery. Methods: A Schiff base was designed to connect oxidized polymeric backbone to DA and both AlgOX and AlgOX-DA were characterized in terms of Raman, XPS, FT-IR, and <sup>1</sup>H- NMR spectroscopies, as well as in vitro mucoadhesive and release tests. Results: Data demonstrated that AlgOX-DA was the most mucoadhesive material among the tested ones and it released the neurotransmitter in simulated nasal fluid and in low amounts in phosphate buffer saline. Results also demonstrated the capability of scanning near-field optical microscopy to study the structural and fluorescence properties of AlgOX, fluorescently labeled with fluorescein isothiocyanate microstructures. Interestingly, in SH-SY5Y neuroblastoma cell line up to 100 μg/mL, no toxic effect was derived from AlgOX and AlgOX-DA in 24 h. Conclusions: Overall, the in vitro performances of AlgOX and AlgOX-DA conjugates seem to encourage further ex vivo and in vivo studies in view of nose-to-brain administration.https://www.mdpi.com/1996-1944/14/13/3495dopamineoxidized alginatemucoadhesionmicroscopycell viability |
| spellingShingle | Adriana Trapani Filomena Corbo Gennaro Agrimi Nicoletta Ditaranto Nicola Cioffi Filippo Perna Andrea Quivelli Erika Stefàno Paola Lunetti Antonella Muscella Santo Marsigliante Antonio Cricenti Marco Luce Cristina Mormile Antonino Cataldo Stefano Bellucci Oxidized Alginate Dopamine Conjugate: In Vitro Characterization for Nose-to-Brain Delivery Application Materials dopamine oxidized alginate mucoadhesion microscopy cell viability |
| title | Oxidized Alginate Dopamine Conjugate: In Vitro Characterization for Nose-to-Brain Delivery Application |
| title_full | Oxidized Alginate Dopamine Conjugate: In Vitro Characterization for Nose-to-Brain Delivery Application |
| title_fullStr | Oxidized Alginate Dopamine Conjugate: In Vitro Characterization for Nose-to-Brain Delivery Application |
| title_full_unstemmed | Oxidized Alginate Dopamine Conjugate: In Vitro Characterization for Nose-to-Brain Delivery Application |
| title_short | Oxidized Alginate Dopamine Conjugate: In Vitro Characterization for Nose-to-Brain Delivery Application |
| title_sort | oxidized alginate dopamine conjugate in vitro characterization for nose to brain delivery application |
| topic | dopamine oxidized alginate mucoadhesion microscopy cell viability |
| url | https://www.mdpi.com/1996-1944/14/13/3495 |
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