Adriana Trapani1, Filomena Corbo1, Gennaro Agrimi2, Nicoletta Ditaranto3, Nicola Cioffi3, Filippo Perna1, Andrea Quivelli1,4, Erika Stefàno5, Paola Lunetti5, Antonella Muscella5, Santo Marsigliante5, Antonio Cricenti6, Marco Luce6, Cristina Mormile7,8, Antonino Cataldo7, Stefano Bellucci7. 1. Department of Pharmacy-Drug Sciences, University of Bari "Aldo Moro", I-70125 Bari, Italy. 2. Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari "Aldo Moro", I-70125 Bari, Italy. 3. Dipartimento di Chimica and CSGI-Bari Unit, Università degli Studi di Bari Aldo Moro, I-70125 Bari, Italy. 4. Consorzio C.I.N.M.P.I.S., Via E. Orabona 4, I-70125 Bari, Italy. 5. Dipartimento Scienze e Tecnologie Biologiche e Ambientali, University of Salento, I-73100 Lecce, Italy. 6. ISM-CNR, Via del Fosso del Cavaliere 100, I-00133 Rome, Italy. 7. Istituto Nazionale di Fisica Nucleare-Laboratori Nazionali di Frascati, Via Enrico Fermi 54, Frascati, I-00044 Rome, Italy. 8. Department of Chemical Science and Technologies, University of Rome Tor Vergata, Via della Ricerca Scientifica 1, I-00133 Rome, Italy.
Abstract
BACKGROUND: The blood-brain barrier (BBB) bypass of dopamine (DA) is still a challenge for supplying it to the neurons of Substantia Nigra 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 1H- 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.
class="abstract_title">BACKGROUND: The blood-brain barrier (BBB) bypass of n class="Chemical">dopamine (DA) is still a challenge for supplying it to the neurons of Substantia Nigra 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 andAlgOX-DA were characterized in terms of Raman, XPS, FT-IR, and1H- 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-SY5Yneuroblastoma cell line up to 100 μg/mL, no toxic effect was derived from AlgOX andAlgOX-DA in 24 h. CONCLUSIONS: Overall, the in vitro performances of AlgOX andAlgOX-DA conjugates seem to encourage further ex vivo and in vivo studies in view of nose-to-brain administration.
Authors: Mohammad A S Abourehab; Rahul R Rajendran; Anshul Singh; Sheersha Pramanik; Prachi Shrivastav; Mohammad Javed Ansari; Ravi Manne; Larissa Souza Amaral; A Deepak Journal: Int J Mol Sci Date: 2022-08-12 Impact factor: 6.208