Development of multifunctional lipid nanocapsules for the co-delivery of paclitaxel and CpG-ODN in the treatment of glioblastoma

Autores
Lollo, Giovanna; Vincent, Marie; Ullio Gamboa, Gabriela Veronica; Lemaire, Laurent; Franconi, Florence; Couez, Dominique; Benoit, Jean Pierre
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In this work, multifunctional lipid nanocapsules (M-LNC) were designed to combine the activity of the cytotoxic drug paclitaxel (PTX) with the immunostimulant CpG. This nanosystem, consisting of modified lipid nanocapsules coated with a cationic polymeric shell composed of chitosan (CS), was able to allocate the hydrophobic drug PTX in the inner oily core, and to associate onto the surface the genetic material CpG. The CS-coated LNC (CS-LNC), showed a narrow size distribution with an average size of 70 nm and a positive zeta potential (+25 mV). They encapsulated PTX in a high amount (98%), and, due to the cationic surface charge, were able to adsorb CpG without losing stability. As a preliminary in vitro study, the apoptotic effect on GL261 glioma cells was investigated. The drug-loaded CS-LNC exhibited the ability to interact with glioma cells and induce an important apoptotic effect in comparison with blank systems. Finally, the M-LNC made of CS-LNC loaded with both CpG and PTX were tested in vivo, injected via convention enhanced delivery (CED) in GL261-glioma-bearing mice. The results showed that the overall survival of mice treated with the M-LNC was significantly increased in comparison with the control, Taxol®, or the separated injection of PTX-loaded LNC and CpG. This effect was also confirmed by magnetic resonance imaging (MRI) which revealed the reduction of tumor growth in the animals treated with CpG and PTX-loaded M-LNC. All these findings suggested that the developed M-LNC could potentiate both CpG immunopotency and PTX antitumor activity by enhancing its delivery into the tumor microenvironment.
Fil: Lollo, Giovanna. Inserm; Francia. Université Nantes Angers Le Mans; Francia
Fil: Vincent, Marie. Inserm; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Ullio Gamboa, Gabriela Veronica. Inserm; Francia. Université Nantes Angers Le Mans; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina
Fil: Lemaire, Laurent. Inserm; Francia. Université Nantes Angers Le Mans; Francia
Fil: Franconi, Florence. Université Nantes Angers Le Mans; Francia
Fil: Couez, Dominique. Inserm; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Benoit, Jean Pierre. Université Nantes Angers Le Mans; Francia. Inserm; Francia
Materia
ANTITUMOR DRUGS
CPG
GLIOBLASTOMA
LIPID NANOCAPSULES
NANOTECHNOLOGY
PACLITAXEL
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/62984
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/62984
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Development of multifunctional lipid nanocapsules for the co-delivery of paclitaxel and CpG-ODN in the treatment of glioblastomaLollo, GiovannaVincent, MarieUllio Gamboa, Gabriela VeronicaLemaire, LaurentFranconi, FlorenceCouez, DominiqueBenoit, Jean PierreANTITUMOR DRUGSCPGGLIOBLASTOMALIPID NANOCAPSULESNANOTECHNOLOGYPACLITAXELhttps://purl.org/becyt/ford/2.10https://purl.org/becyt/ford/2In this work, multifunctional lipid nanocapsules (M-LNC) were designed to combine the activity of the cytotoxic drug paclitaxel (PTX) with the immunostimulant CpG. This nanosystem, consisting of modified lipid nanocapsules coated with a cationic polymeric shell composed of chitosan (CS), was able to allocate the hydrophobic drug PTX in the inner oily core, and to associate onto the surface the genetic material CpG. The CS-coated LNC (CS-LNC), showed a narrow size distribution with an average size of 70 nm and a positive zeta potential (+25 mV). They encapsulated PTX in a high amount (98%), and, due to the cationic surface charge, were able to adsorb CpG without losing stability. As a preliminary in vitro study, the apoptotic effect on GL261 glioma cells was investigated. The drug-loaded CS-LNC exhibited the ability to interact with glioma cells and induce an important apoptotic effect in comparison with blank systems. Finally, the M-LNC made of CS-LNC loaded with both CpG and PTX were tested in vivo, injected via convention enhanced delivery (CED) in GL261-glioma-bearing mice. The results showed that the overall survival of mice treated with the M-LNC was significantly increased in comparison with the control, Taxol®, or the separated injection of PTX-loaded LNC and CpG. This effect was also confirmed by magnetic resonance imaging (MRI) which revealed the reduction of tumor growth in the animals treated with CpG and PTX-loaded M-LNC. All these findings suggested that the developed M-LNC could potentiate both CpG immunopotency and PTX antitumor activity by enhancing its delivery into the tumor microenvironment.Fil: Lollo, Giovanna. Inserm; Francia. Université Nantes Angers Le Mans; FranciaFil: Vincent, Marie. Inserm; Francia. Centre National de la Recherche Scientifique; FranciaFil: Ullio Gamboa, Gabriela Veronica. Inserm; Francia. Université Nantes Angers Le Mans; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; ArgentinaFil: Lemaire, Laurent. Inserm; Francia. Université Nantes Angers Le Mans; FranciaFil: Franconi, Florence. Université Nantes Angers Le Mans; FranciaFil: Couez, Dominique. Inserm; Francia. Centre National de la Recherche Scientifique; FranciaFil: Benoit, Jean Pierre. Université Nantes Angers Le Mans; Francia. Inserm; FranciaElsevier Science2015-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/62984Lollo, Giovanna; Vincent, Marie; Ullio Gamboa, Gabriela Veronica; Lemaire, Laurent; Franconi, Florence; et al.; Development of multifunctional lipid nanocapsules for the co-delivery of paclitaxel and CpG-ODN in the treatment of glioblastoma; Elsevier Science; International Journal Of Pharmaceutics; 495; 2; 11-2015; 972-9800378-5173CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.ijpharm.2015.09.062info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S037851731530260Xinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:03:32Zoai:ri.conicet.gov.ar:11336/62984instacron: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 12:03:33.212CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Development of multifunctional lipid nanocapsules for the co-delivery of paclitaxel and CpG-ODN in the treatment of glioblastoma
title Development of multifunctional lipid nanocapsules for the co-delivery of paclitaxel and CpG-ODN in the treatment of glioblastoma
spellingShingle Development of multifunctional lipid nanocapsules for the co-delivery of paclitaxel and CpG-ODN in the treatment of glioblastoma
Lollo, Giovanna
ANTITUMOR DRUGS
CPG
GLIOBLASTOMA
LIPID NANOCAPSULES
NANOTECHNOLOGY
PACLITAXEL
title_short Development of multifunctional lipid nanocapsules for the co-delivery of paclitaxel and CpG-ODN in the treatment of glioblastoma
title_full Development of multifunctional lipid nanocapsules for the co-delivery of paclitaxel and CpG-ODN in the treatment of glioblastoma
title_fullStr Development of multifunctional lipid nanocapsules for the co-delivery of paclitaxel and CpG-ODN in the treatment of glioblastoma
title_full_unstemmed Development of multifunctional lipid nanocapsules for the co-delivery of paclitaxel and CpG-ODN in the treatment of glioblastoma
title_sort Development of multifunctional lipid nanocapsules for the co-delivery of paclitaxel and CpG-ODN in the treatment of glioblastoma
dc.creator.none.fl_str_mv Lollo, Giovanna
Vincent, Marie
Ullio Gamboa, Gabriela Veronica
Lemaire, Laurent
Franconi, Florence
Couez, Dominique
Benoit, Jean Pierre
author Lollo, Giovanna
author_facet Lollo, Giovanna
Vincent, Marie
Ullio Gamboa, Gabriela Veronica
Lemaire, Laurent
Franconi, Florence
Couez, Dominique
Benoit, Jean Pierre
author_role author
author2 Vincent, Marie
Ullio Gamboa, Gabriela Veronica
Lemaire, Laurent
Franconi, Florence
Couez, Dominique
Benoit, Jean Pierre
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv ANTITUMOR DRUGS
CPG
GLIOBLASTOMA
LIPID NANOCAPSULES
NANOTECHNOLOGY
PACLITAXEL
topic ANTITUMOR DRUGS
CPG
GLIOBLASTOMA
LIPID NANOCAPSULES
NANOTECHNOLOGY
PACLITAXEL
purl_subject.fl_str_mv https://purl.org/becyt/ford/2.10
https://purl.org/becyt/ford/2
dc.description.none.fl_txt_mv In this work, multifunctional lipid nanocapsules (M-LNC) were designed to combine the activity of the cytotoxic drug paclitaxel (PTX) with the immunostimulant CpG. This nanosystem, consisting of modified lipid nanocapsules coated with a cationic polymeric shell composed of chitosan (CS), was able to allocate the hydrophobic drug PTX in the inner oily core, and to associate onto the surface the genetic material CpG. The CS-coated LNC (CS-LNC), showed a narrow size distribution with an average size of 70 nm and a positive zeta potential (+25 mV). They encapsulated PTX in a high amount (98%), and, due to the cationic surface charge, were able to adsorb CpG without losing stability. As a preliminary in vitro study, the apoptotic effect on GL261 glioma cells was investigated. The drug-loaded CS-LNC exhibited the ability to interact with glioma cells and induce an important apoptotic effect in comparison with blank systems. Finally, the M-LNC made of CS-LNC loaded with both CpG and PTX were tested in vivo, injected via convention enhanced delivery (CED) in GL261-glioma-bearing mice. The results showed that the overall survival of mice treated with the M-LNC was significantly increased in comparison with the control, Taxol®, or the separated injection of PTX-loaded LNC and CpG. This effect was also confirmed by magnetic resonance imaging (MRI) which revealed the reduction of tumor growth in the animals treated with CpG and PTX-loaded M-LNC. All these findings suggested that the developed M-LNC could potentiate both CpG immunopotency and PTX antitumor activity by enhancing its delivery into the tumor microenvironment.
Fil: Lollo, Giovanna. Inserm; Francia. Université Nantes Angers Le Mans; Francia
Fil: Vincent, Marie. Inserm; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Ullio Gamboa, Gabriela Veronica. Inserm; Francia. Université Nantes Angers Le Mans; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina
Fil: Lemaire, Laurent. Inserm; Francia. Université Nantes Angers Le Mans; Francia
Fil: Franconi, Florence. Université Nantes Angers Le Mans; Francia
Fil: Couez, Dominique. Inserm; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Benoit, Jean Pierre. Université Nantes Angers Le Mans; Francia. Inserm; Francia
description In this work, multifunctional lipid nanocapsules (M-LNC) were designed to combine the activity of the cytotoxic drug paclitaxel (PTX) with the immunostimulant CpG. This nanosystem, consisting of modified lipid nanocapsules coated with a cationic polymeric shell composed of chitosan (CS), was able to allocate the hydrophobic drug PTX in the inner oily core, and to associate onto the surface the genetic material CpG. The CS-coated LNC (CS-LNC), showed a narrow size distribution with an average size of 70 nm and a positive zeta potential (+25 mV). They encapsulated PTX in a high amount (98%), and, due to the cationic surface charge, were able to adsorb CpG without losing stability. As a preliminary in vitro study, the apoptotic effect on GL261 glioma cells was investigated. The drug-loaded CS-LNC exhibited the ability to interact with glioma cells and induce an important apoptotic effect in comparison with blank systems. Finally, the M-LNC made of CS-LNC loaded with both CpG and PTX were tested in vivo, injected via convention enhanced delivery (CED) in GL261-glioma-bearing mice. The results showed that the overall survival of mice treated with the M-LNC was significantly increased in comparison with the control, Taxol®, or the separated injection of PTX-loaded LNC and CpG. This effect was also confirmed by magnetic resonance imaging (MRI) which revealed the reduction of tumor growth in the animals treated with CpG and PTX-loaded M-LNC. All these findings suggested that the developed M-LNC could potentiate both CpG immunopotency and PTX antitumor activity by enhancing its delivery into the tumor microenvironment.
publishDate 2015
dc.date.none.fl_str_mv 2015-11
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/11336/62984
Lollo, Giovanna; Vincent, Marie; Ullio Gamboa, Gabriela Veronica; Lemaire, Laurent; Franconi, Florence; et al.; Development of multifunctional lipid nanocapsules for the co-delivery of paclitaxel and CpG-ODN in the treatment of glioblastoma; Elsevier Science; International Journal Of Pharmaceutics; 495; 2; 11-2015; 972-980
0378-5173
CONICET Digital
CONICET
url http://hdl.handle.net/11336/62984
identifier_str_mv Lollo, Giovanna; Vincent, Marie; Ullio Gamboa, Gabriela Veronica; Lemaire, Laurent; Franconi, Florence; et al.; Development of multifunctional lipid nanocapsules for the co-delivery of paclitaxel and CpG-ODN in the treatment of glioblastoma; Elsevier Science; International Journal Of Pharmaceutics; 495; 2; 11-2015; 972-980
0378-5173
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ijpharm.2015.09.062
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S037851731530260X
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science
publisher.none.fl_str_mv Elsevier Science
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
_version_ 1846782378500947968
score 12.982451

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