Crosslinked casein-based micelles as a dually responsive drug delivery system

Autores
Picchio, Matías Luis; Cuggino, Julio César; Nagel, Gregor; Wedepohl, Stefanie; Minari, Roque Javier; Alvarez Igarzabal, Cecilia Ines; Gugliotta, Luis Marcelino; Calderon, Marcelo
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
New types of biodegradable nanocarriers for drug delivery were prepared using casein (CAS) micelles as particle templates and glyceraldehyde (GAL) as a crosslinking agent. We found that highly crosslinked casein micelles (CCM) maintained their structural integrity at pH 7.4 (plasma conditions) but were easily degraded in the presence of proteases at pH 5 (lysosomal conditions). Nile red (NR) was chosen as a hydrophobic model drug inspired by the natural role of casein as lipophilic nutrient nanotransporter. The cumulative release of the NR-loaded micelles showed marginal dye leakage at pH 7.4 but was significantly accelerated by protease and pH-mediated degradation of the nanocarriers in a dual-responsive fashion. The prepared nanocarriers possess many favorable features for drug delivery: excellent biocompatibility and biodegradability, high stability in physiological conditions, remarkable capacity for the encapsulation of hydrophobic drugs, minimal drug leakage under extracellular conditions, and rapid drug release in response to the endo-lysosomal levels of pH and proteases. In this regard, the prepared CCM represent a promising candidate for the delivery and triggered release of anti-cancer drugs in lysosomal environments.
Fil: Picchio, Matías Luis. Universidad Nacional de Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada; Argentina
Fil: Cuggino, Julio César. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina
Fil: Nagel, Gregor. Freie Universitat Berlin; Alemania
Fil: Wedepohl, Stefanie. Freie Universitat Berlin; Alemania
Fil: Minari, Roque Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina
Fil: Alvarez Igarzabal, Cecilia Ines. Universidad Nacional de Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada; Argentina. Freie Universitat Berlin; Alemania
Fil: Gugliotta, Luis Marcelino. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina
Fil: Calderon, Marcelo. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; Argentina. Freie Universitat Berlin; Alemania
Materia
Casein micelles
Drug delivery
Crosslinking
Hydrophobic drug
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/90941
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/90941
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Crosslinked casein-based micelles as a dually responsive drug delivery systemPicchio, Matías LuisCuggino, Julio CésarNagel, GregorWedepohl, StefanieMinari, Roque JavierAlvarez Igarzabal, Cecilia InesGugliotta, Luis MarcelinoCalderon, MarceloCasein micellesDrug deliveryCrosslinkingHydrophobic drughttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1https://purl.org/becyt/ford/2.10https://purl.org/becyt/ford/2https://purl.org/becyt/ford/2.5https://purl.org/becyt/ford/2New types of biodegradable nanocarriers for drug delivery were prepared using casein (CAS) micelles as particle templates and glyceraldehyde (GAL) as a crosslinking agent. We found that highly crosslinked casein micelles (CCM) maintained their structural integrity at pH 7.4 (plasma conditions) but were easily degraded in the presence of proteases at pH 5 (lysosomal conditions). Nile red (NR) was chosen as a hydrophobic model drug inspired by the natural role of casein as lipophilic nutrient nanotransporter. The cumulative release of the NR-loaded micelles showed marginal dye leakage at pH 7.4 but was significantly accelerated by protease and pH-mediated degradation of the nanocarriers in a dual-responsive fashion. The prepared nanocarriers possess many favorable features for drug delivery: excellent biocompatibility and biodegradability, high stability in physiological conditions, remarkable capacity for the encapsulation of hydrophobic drugs, minimal drug leakage under extracellular conditions, and rapid drug release in response to the endo-lysosomal levels of pH and proteases. In this regard, the prepared CCM represent a promising candidate for the delivery and triggered release of anti-cancer drugs in lysosomal environments.Fil: Picchio, Matías Luis. Universidad Nacional de Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada; ArgentinaFil: Cuggino, Julio César. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Nagel, Gregor. Freie Universitat Berlin; AlemaniaFil: Wedepohl, Stefanie. Freie Universitat Berlin; AlemaniaFil: Minari, Roque Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Alvarez Igarzabal, Cecilia Ines. Universidad Nacional de Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada; Argentina. Freie Universitat Berlin; AlemaniaFil: Gugliotta, Luis Marcelino. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Calderon, Marcelo. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; Argentina. Freie Universitat Berlin; AlemaniaRoyal Society of Chemistry2018-07-30info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/90941Picchio, Matías Luis; Cuggino, Julio César; Nagel, Gregor; Wedepohl, Stefanie; Minari, Roque Javier; et al.; Crosslinked casein-based micelles as a dually responsive drug delivery system; Royal Society of Chemistry; Polymer Chemistry; 9; 25; 30-7-2018; 3499-35101759-99621759-9954CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://pubs.rsc.org/en/Content/ArticleLanding/2018/PY/C8PY00600Hinfo:eu-repo/semantics/altIdentifier/doi/10.1039/C8PY00600Hinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:59:13Zoai:ri.conicet.gov.ar:11336/90941instacron: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:34982025-09-03 09:59:13.627CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Crosslinked casein-based micelles as a dually responsive drug delivery system
title Crosslinked casein-based micelles as a dually responsive drug delivery system
spellingShingle Crosslinked casein-based micelles as a dually responsive drug delivery system
Picchio, Matías Luis
Casein micelles
Drug delivery
Crosslinking
Hydrophobic drug
title_short Crosslinked casein-based micelles as a dually responsive drug delivery system
title_full Crosslinked casein-based micelles as a dually responsive drug delivery system
title_fullStr Crosslinked casein-based micelles as a dually responsive drug delivery system
title_full_unstemmed Crosslinked casein-based micelles as a dually responsive drug delivery system
title_sort Crosslinked casein-based micelles as a dually responsive drug delivery system
dc.creator.none.fl_str_mv Picchio, Matías Luis
Cuggino, Julio César
Nagel, Gregor
Wedepohl, Stefanie
Minari, Roque Javier
Alvarez Igarzabal, Cecilia Ines
Gugliotta, Luis Marcelino
Calderon, Marcelo
author Picchio, Matías Luis
author_facet Picchio, Matías Luis
Cuggino, Julio César
Nagel, Gregor
Wedepohl, Stefanie
Minari, Roque Javier
Alvarez Igarzabal, Cecilia Ines
Gugliotta, Luis Marcelino
Calderon, Marcelo
author_role author
author2 Cuggino, Julio César
Nagel, Gregor
Wedepohl, Stefanie
Minari, Roque Javier
Alvarez Igarzabal, Cecilia Ines
Gugliotta, Luis Marcelino
Calderon, Marcelo
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Casein micelles
Drug delivery
Crosslinking
Hydrophobic drug
topic Casein micelles
Drug delivery
Crosslinking
Hydrophobic drug
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/2.10
https://purl.org/becyt/ford/2
https://purl.org/becyt/ford/2.5
https://purl.org/becyt/ford/2
dc.description.none.fl_txt_mv New types of biodegradable nanocarriers for drug delivery were prepared using casein (CAS) micelles as particle templates and glyceraldehyde (GAL) as a crosslinking agent. We found that highly crosslinked casein micelles (CCM) maintained their structural integrity at pH 7.4 (plasma conditions) but were easily degraded in the presence of proteases at pH 5 (lysosomal conditions). Nile red (NR) was chosen as a hydrophobic model drug inspired by the natural role of casein as lipophilic nutrient nanotransporter. The cumulative release of the NR-loaded micelles showed marginal dye leakage at pH 7.4 but was significantly accelerated by protease and pH-mediated degradation of the nanocarriers in a dual-responsive fashion. The prepared nanocarriers possess many favorable features for drug delivery: excellent biocompatibility and biodegradability, high stability in physiological conditions, remarkable capacity for the encapsulation of hydrophobic drugs, minimal drug leakage under extracellular conditions, and rapid drug release in response to the endo-lysosomal levels of pH and proteases. In this regard, the prepared CCM represent a promising candidate for the delivery and triggered release of anti-cancer drugs in lysosomal environments.
Fil: Picchio, Matías Luis. Universidad Nacional de Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada; Argentina
Fil: Cuggino, Julio César. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina
Fil: Nagel, Gregor. Freie Universitat Berlin; Alemania
Fil: Wedepohl, Stefanie. Freie Universitat Berlin; Alemania
Fil: Minari, Roque Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina
Fil: Alvarez Igarzabal, Cecilia Ines. Universidad Nacional de Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada; Argentina. Freie Universitat Berlin; Alemania
Fil: Gugliotta, Luis Marcelino. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina
Fil: Calderon, Marcelo. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; Argentina. Freie Universitat Berlin; Alemania
description New types of biodegradable nanocarriers for drug delivery were prepared using casein (CAS) micelles as particle templates and glyceraldehyde (GAL) as a crosslinking agent. We found that highly crosslinked casein micelles (CCM) maintained their structural integrity at pH 7.4 (plasma conditions) but were easily degraded in the presence of proteases at pH 5 (lysosomal conditions). Nile red (NR) was chosen as a hydrophobic model drug inspired by the natural role of casein as lipophilic nutrient nanotransporter. The cumulative release of the NR-loaded micelles showed marginal dye leakage at pH 7.4 but was significantly accelerated by protease and pH-mediated degradation of the nanocarriers in a dual-responsive fashion. The prepared nanocarriers possess many favorable features for drug delivery: excellent biocompatibility and biodegradability, high stability in physiological conditions, remarkable capacity for the encapsulation of hydrophobic drugs, minimal drug leakage under extracellular conditions, and rapid drug release in response to the endo-lysosomal levels of pH and proteases. In this regard, the prepared CCM represent a promising candidate for the delivery and triggered release of anti-cancer drugs in lysosomal environments.
publishDate 2018
dc.date.none.fl_str_mv 2018-07-30
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/11336/90941
Picchio, Matías Luis; Cuggino, Julio César; Nagel, Gregor; Wedepohl, Stefanie; Minari, Roque Javier; et al.; Crosslinked casein-based micelles as a dually responsive drug delivery system; Royal Society of Chemistry; Polymer Chemistry; 9; 25; 30-7-2018; 3499-3510
1759-9962
1759-9954
CONICET Digital
CONICET
url http://hdl.handle.net/11336/90941
identifier_str_mv Picchio, Matías Luis; Cuggino, Julio César; Nagel, Gregor; Wedepohl, Stefanie; Minari, Roque Javier; et al.; Crosslinked casein-based micelles as a dually responsive drug delivery system; Royal Society of Chemistry; Polymer Chemistry; 9; 25; 30-7-2018; 3499-3510
1759-9962
1759-9954
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://pubs.rsc.org/en/Content/ArticleLanding/2018/PY/C8PY00600H
info:eu-repo/semantics/altIdentifier/doi/10.1039/C8PY00600H
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Royal Society of Chemistry
publisher.none.fl_str_mv Royal Society of Chemistry
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 13.13397

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