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| Pàgina inicial > Articles > Articles publicats > Bioinspired theranostic coordination polymer nanoparticles for intranasal dopamine replacement in parkinson's disease |
(Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular) (Universitat Autònoma de Barcelona. Departament de Química) (Institut Català de Nanociència i Nanotecnologia) (Institut Català de Nanociència i Nanotecnologia) (Universitat Autònoma de Barcelona. Servei de Ressonància Magnètica Nuclear) (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí") (Hospital Universitari Vall d'Hebron. Institut de Recerca) (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular) (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí") (Institut Català de Nanociència i Nanotecnologia)
| Data: | 2021 |
| Resum: | Dopamine (DA) is one of the main neurotransmitters found in the central nervous system and has a vital role in the function of dopaminergic (DArgic) neurons. A progressive loss of this specific subset of cells is one of the hallmarks of age-related neurodegenerative disorders such as Parkinson's disease (PD). Symptomatic therapy for PD has been centered in the precursor l-DOPA administration, an amino acid precursor of DA that crosses the blood-brain barrier (BBB) while DA does not, although this approach presents medium- to long-term side effects. To overcome this limitation, DA-nanoencapsulation therapies are actively being searched as an alternative for DA replacement. However, overcoming the low yield of encapsulation and/or poor biodistribution/bioavailability of DA is still a current challenge. Herein, we report the synthesis of a family of neuromelanin bioinspired polymeric nanoparticles. Our system is based on the encapsulation of DA within nanoparticles through its reversible coordination complexation to iron metal nodes polymerized with a bis-imidazol ligand. Our methodology, in addition to being simple and inexpensive, results in DA loading efficiencies of up to 60%. In vitro, DA nanoscale coordination polymers (DA-NCPs) exhibited lower toxicity, degradation kinetics, and enhanced uptake by BE(2)-M17 DArgic cells compared to free DA. Direct infusion of the particles in the ventricle of rats in vivo showed a rapid distribution within the brain of healthy rats, leading to an increase in striatal DA levels. More importantly, after 4 days of nasal administrations with DA-NCPs equivalent to 200 μg of the free drug per day, the number and duration of apomorphine-induced rotations was significantly lower from that in either vehicle or DA-treated rats performed for comparison purposes. Overall, this study demonstrates the advantages of using nanostructured DA for DA-replacement therapy. |
| Ajuts: | European Commission 777222 Agencia Estatal de Investigación RTI2018-098027-B-C21 Agencia Estatal de Investigación RTI2018-098027-B-C22 Agencia Estatal de Investigación SEV-2017-0706 Ministerio de Economía y Competitividad SAF2016-77541-R |
| Nota: | Altres ajuts: the ICN2 is funded by the CERCA program/Generalitat de Catalunya. The authors thank the support from COST Action CA17121. |
| Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Llengua: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Matèria: | Neuromelanin ; Dopamine ; Parkinson's disease ; Neurodegeneration ; Coordination polymers |
| Publicat a: | ACS nano, Vol. 15, issue 5 (May 2021) , p. 8592-8609, ISSN 1936-086X |
