Bioinspired theranostic coordination polymer nanoparticles for intranasal dopamine replacement in parkinson's disease
- Autores
- García Pardo, Javier; Novio, Fernando; Nador, Fabiana Gabriela; Cavaliere, Ivana; Suárez García, Salvio; Lope Piedrafita, Silvia; Candiota, Ana Paula; Romero Gimenez, Jordi; Rodríguez Galván, Beatriz; Bové, Jordi; Vila, Miquel; Lorenzo, Julia; Ruiz Molina, Daniel
- Año de publicación
- 2021
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- 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.
Fil: García Pardo, Javier. Universitat Autònoma de Barcelona; España
Fil: Novio, Fernando. Universitat Autònoma de Barcelona; España
Fil: Nador, Fabiana Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina
Fil: Cavaliere, Ivana. Consejo Superior de Investigaciones Científicas; España
Fil: Suárez García, Salvio. Universitat Autònoma de Barcelona; España
Fil: Lope Piedrafita, Silvia. Universitat Autònoma de Barcelona; España
Fil: Candiota, Ana Paula. Universitat Autònoma de Barcelona; España
Fil: Romero Gimenez, Jordi. Consejo Superior de Investigaciones Científicas; España
Fil: Rodríguez Galván, Beatriz. Universitat Autònoma de Barcelona; España
Fil: Bové, Jordi. Consejo Superior de Investigaciones Científicas; España
Fil: Vila, Miquel. Universitat Autònoma de Barcelona; España
Fil: Lorenzo, Julia. Universitat Autònoma de Barcelona; España
Fil: Ruiz Molina, Daniel. No especifíca; - Materia
-
COORDINATION POLYMERS
DOPAMINE
NEURODEGENERATION
NEUROMELANIN
PARKINSON'S DISEASE - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/211423
Ver los metadatos del registro completo
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Bioinspired theranostic coordination polymer nanoparticles for intranasal dopamine replacement in parkinson's diseaseGarcía Pardo, JavierNovio, FernandoNador, Fabiana GabrielaCavaliere, IvanaSuárez García, SalvioLope Piedrafita, SilviaCandiota, Ana PaulaRomero Gimenez, JordiRodríguez Galván, BeatrizBové, JordiVila, MiquelLorenzo, JuliaRuiz Molina, DanielCOORDINATION POLYMERSDOPAMINENEURODEGENERATIONNEUROMELANINPARKINSON'S DISEASEhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Dopamine (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.Fil: García Pardo, Javier. Universitat Autònoma de Barcelona; EspañaFil: Novio, Fernando. Universitat Autònoma de Barcelona; EspañaFil: Nador, Fabiana Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: Cavaliere, Ivana. Consejo Superior de Investigaciones Científicas; EspañaFil: Suárez García, Salvio. Universitat Autònoma de Barcelona; EspañaFil: Lope Piedrafita, Silvia. Universitat Autònoma de Barcelona; EspañaFil: Candiota, Ana Paula. Universitat Autònoma de Barcelona; EspañaFil: Romero Gimenez, Jordi. Consejo Superior de Investigaciones Científicas; EspañaFil: Rodríguez Galván, Beatriz. Universitat Autònoma de Barcelona; EspañaFil: Bové, Jordi. Consejo Superior de Investigaciones Científicas; EspañaFil: Vila, Miquel. Universitat Autònoma de Barcelona; EspañaFil: Lorenzo, Julia. Universitat Autònoma de Barcelona; EspañaFil: Ruiz Molina, Daniel. No especifíca;American Chemical Society2021-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/211423García Pardo, Javier; Novio, Fernando; Nador, Fabiana Gabriela; Cavaliere, Ivana; Suárez García, Salvio; et al.; Bioinspired theranostic coordination polymer nanoparticles for intranasal dopamine replacement in parkinson's disease; American Chemical Society; ACS Nano; 15; 5; 5-2021; 8592-86091936-0851CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/10.1021/acsnano.1c00453info:eu-repo/semantics/altIdentifier/doi/10.1021/acsnano.1c00453info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:23:11Zoai:ri.conicet.gov.ar:11336/211423instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:23:11.269CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Bioinspired theranostic coordination polymer nanoparticles for intranasal dopamine replacement in parkinson's disease |
title |
Bioinspired theranostic coordination polymer nanoparticles for intranasal dopamine replacement in parkinson's disease |
spellingShingle |
Bioinspired theranostic coordination polymer nanoparticles for intranasal dopamine replacement in parkinson's disease García Pardo, Javier COORDINATION POLYMERS DOPAMINE NEURODEGENERATION NEUROMELANIN PARKINSON'S DISEASE |
title_short |
Bioinspired theranostic coordination polymer nanoparticles for intranasal dopamine replacement in parkinson's disease |
title_full |
Bioinspired theranostic coordination polymer nanoparticles for intranasal dopamine replacement in parkinson's disease |
title_fullStr |
Bioinspired theranostic coordination polymer nanoparticles for intranasal dopamine replacement in parkinson's disease |
title_full_unstemmed |
Bioinspired theranostic coordination polymer nanoparticles for intranasal dopamine replacement in parkinson's disease |
title_sort |
Bioinspired theranostic coordination polymer nanoparticles for intranasal dopamine replacement in parkinson's disease |
dc.creator.none.fl_str_mv |
García Pardo, Javier Novio, Fernando Nador, Fabiana Gabriela Cavaliere, Ivana Suárez García, Salvio Lope Piedrafita, Silvia Candiota, Ana Paula Romero Gimenez, Jordi Rodríguez Galván, Beatriz Bové, Jordi Vila, Miquel Lorenzo, Julia Ruiz Molina, Daniel |
author |
García Pardo, Javier |
author_facet |
García Pardo, Javier Novio, Fernando Nador, Fabiana Gabriela Cavaliere, Ivana Suárez García, Salvio Lope Piedrafita, Silvia Candiota, Ana Paula Romero Gimenez, Jordi Rodríguez Galván, Beatriz Bové, Jordi Vila, Miquel Lorenzo, Julia Ruiz Molina, Daniel |
author_role |
author |
author2 |
Novio, Fernando Nador, Fabiana Gabriela Cavaliere, Ivana Suárez García, Salvio Lope Piedrafita, Silvia Candiota, Ana Paula Romero Gimenez, Jordi Rodríguez Galván, Beatriz Bové, Jordi Vila, Miquel Lorenzo, Julia Ruiz Molina, Daniel |
author2_role |
author author author author author author author author author author author author |
dc.subject.none.fl_str_mv |
COORDINATION POLYMERS DOPAMINE NEURODEGENERATION NEUROMELANIN PARKINSON'S DISEASE |
topic |
COORDINATION POLYMERS DOPAMINE NEURODEGENERATION NEUROMELANIN PARKINSON'S DISEASE |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
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. Fil: García Pardo, Javier. Universitat Autònoma de Barcelona; España Fil: Novio, Fernando. Universitat Autònoma de Barcelona; España Fil: Nador, Fabiana Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina Fil: Cavaliere, Ivana. Consejo Superior de Investigaciones Científicas; España Fil: Suárez García, Salvio. Universitat Autònoma de Barcelona; España Fil: Lope Piedrafita, Silvia. Universitat Autònoma de Barcelona; España Fil: Candiota, Ana Paula. Universitat Autònoma de Barcelona; España Fil: Romero Gimenez, Jordi. Consejo Superior de Investigaciones Científicas; España Fil: Rodríguez Galván, Beatriz. Universitat Autònoma de Barcelona; España Fil: Bové, Jordi. Consejo Superior de Investigaciones Científicas; España Fil: Vila, Miquel. Universitat Autònoma de Barcelona; España Fil: Lorenzo, Julia. Universitat Autònoma de Barcelona; España Fil: Ruiz Molina, Daniel. No especifíca; |
description |
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. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-05 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/211423 García Pardo, Javier; Novio, Fernando; Nador, Fabiana Gabriela; Cavaliere, Ivana; Suárez García, Salvio; et al.; Bioinspired theranostic coordination polymer nanoparticles for intranasal dopamine replacement in parkinson's disease; American Chemical Society; ACS Nano; 15; 5; 5-2021; 8592-8609 1936-0851 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/211423 |
identifier_str_mv |
García Pardo, Javier; Novio, Fernando; Nador, Fabiana Gabriela; Cavaliere, Ivana; Suárez García, Salvio; et al.; Bioinspired theranostic coordination polymer nanoparticles for intranasal dopamine replacement in parkinson's disease; American Chemical Society; ACS Nano; 15; 5; 5-2021; 8592-8609 1936-0851 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/10.1021/acsnano.1c00453 info:eu-repo/semantics/altIdentifier/doi/10.1021/acsnano.1c00453 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
American Chemical Society |
publisher.none.fl_str_mv |
American Chemical Society |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
reponame_str |
CONICET Digital (CONICET) |
collection |
CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.name.fl_str_mv |
CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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score |
13.070432 |