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
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/211423
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/211423
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling 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 Técnicas2025-10-22T11:55:57Zoai: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:34982025-10-22 11:55:58.012CONICET 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)
instname_str 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 12.982451

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