dc.contributor.author |
Garcia-Pardo, Javier |
dc.contributor.author |
Novio Vázquez, Fernando |
dc.contributor.author |
Nador, Fabiana |
dc.contributor.author |
Cavaliere, Ivana |
dc.contributor.author |
Suárez García, Salvio |
dc.contributor.author |
Lope-Piedrafita, Silvia |
dc.contributor.author |
Candiota Silveira, Ana Paula |
dc.contributor.author |
Romero-Gimenez, Jordi |
dc.contributor.author |
Rodríguez-Galván, Beatriz |
dc.contributor.author |
Bové, Jordi |
dc.contributor.author |
Vila Bover, Miquel |
dc.contributor.author |
Lorenzo Rivera, Julia |
dc.contributor.author |
Ruiz-Molina, Daniel |
dc.date |
2021 |
dc.identifier |
https://ddd.uab.cat/record/248670 |
dc.identifier |
urn:10.1021/acsnano.1c00453 |
dc.identifier |
urn:oai:ddd.uab.cat:248670 |
dc.identifier |
urn:scopus_id:85106422905 |
dc.identifier |
urn:articleid:1936086Xv15n5p8592 |
dc.identifier |
urn:oai:egreta.uab.cat:publications/2cacf52b-99b0-4dc5-a4e6-1cc7ec1613df |
dc.identifier |
urn:pmid:33885286 |
dc.identifier |
urn:pmc-uid:8558863 |
dc.identifier |
urn:pmcid:PMC8558863 |
dc.identifier |
urn:oai:pubmedcentral.nih.gov:8558863 |
dc.identifier |
urn:icn2uab:6518417 |
dc.format |
application/pdf |
dc.language |
eng |
dc.publisher |
|
dc.relation |
European Commission 777222 |
dc.relation |
Agencia Estatal de Investigación RTI2018-098027-B-C21 |
dc.relation |
Agencia Estatal de Investigación RTI2018-098027-B-C22 |
dc.relation |
Agencia Estatal de Investigación SEV-2017-0706 |
dc.relation |
Ministerio de Economía y Competitividad SAF2016-77541-R |
dc.relation |
ACS nano ; Vol. 15, issue 5 (May 2021), p. 8592-8609 |
dc.rights |
open access |
dc.rights |
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. |
dc.rights |
https://creativecommons.org/licenses/by/4.0/ |
dc.subject |
Neuromelanin |
dc.subject |
Dopamine |
dc.subject |
Parkinson's disease |
dc.subject |
Neurodegeneration |
dc.subject |
Coordination polymers |
dc.title |
Bioinspired theranostic coordination polymer nanoparticles for intranasal dopamine replacement in parkinson's disease |
dc.type |
Article |
dc.description.abstract |
Altres ajuts: the ICN2 is funded by the CERCA program/Generalitat de Catalunya. The authors thank the support from COST Action CA17121. |
dc.description.abstract |
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. |