Biochemical characterization of the interactions between doxorubicin and lipidic GM1 micelles with or without paclitaxel loading

Autores
Leonhard, Victoria; Alasino, Roxana Valeria; Bianco, Ismael Dario; Garro, Ariel Gustavo; Heredia, Valeria; Beltramo, Dante Miguel
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Doxorubicin (Dox) is an anthracycline anticancer drug with high water solubility, whose use is limited primarily due to significant side effects. In this study it is shown that Dox interacts with monosialoglycosphingolipid (GM1) ganglioside micelles primarily through hydro-phobic interactions independent of pH and ionic strength. In addition, Dox can be incorporated even into GM1 micelles already containing highly hydrophobic paclitaxel (Ptx). However, it was not possible to incorporate Ptx into Dox-containing GM1 micelles, suggesting that Dox could be occupying a more external position in the micelles. This result is in agreement with a higher hydrolysis of Dox than of Ptx when micelles were incubated at alkaline pH. The loading of Dox into GM1 micelles was observed over a broad range of temperature (4°C–55°C). Furthermore, Dox-loaded micelles were stable in aqueous solutions exhibiting no aggregation or precipitation for up to 2 months when kept at 4°C–25°C and even after freeze–thawing cycles. Upon exposure to blood components, Dox-containing micelles were observed to interact with human serum albumin. However, the amount of human serum albumin that ended up being associated to the micelles was inversely related to the amount of Dox, suggesting that both could share their binding sites. In vitro studies on Hep2 cells showed that the cellular uptake and cytotoxic activity of Dox and Ptx from the micellar complexes were similar to those of the free form of these drugs, even when the micelle was covered with albumin. These results support the idea of the existence of different nano-domains in a single micelle and the fact that this micellar model could be used as a platform for loading and delivering hydrophobic and hydrophilic active pharmaceutical ingredients.
Fil: Leonhard, Victoria. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia En Productos y Procesos de Córdoba. Laboratorio de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina
Fil: Alasino, Roxana Valeria. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia En Productos y Procesos de Córdoba. Laboratorio de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina
Fil: Bianco, Ismael Dario. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia En Productos y Procesos de Córdoba. Laboratorio de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Nacional de La Rioja; Argentina
Fil: Garro, Ariel Gustavo. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia En Productos y Procesos de Córdoba. Laboratorio de Biotecnología; Argentina
Fil: Heredia, Valeria. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia En Productos y Procesos de Córdoba. Laboratorio de Biotecnología; Argentina
Fil: Beltramo, Dante Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Católica de Córdoba; Argentina. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia En Productos y Procesos de Córdoba. Laboratorio de Biotecnología; Argentina
Materia
CANCER DRUGS
DRUG DELIVERY
HYDROPHOBIC INTERACTIONS
NANO-DOMAINS
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:11336/180204
Acceder
id CONICETDig_50d519d15c210596e5613bf28f95508e
oai_identifier_str oai:ri.conicet.gov.ar:11336/180204
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Biochemical characterization of the interactions between doxorubicin and lipidic GM1 micelles with or without paclitaxel loadingLeonhard, VictoriaAlasino, Roxana ValeriaBianco, Ismael DarioGarro, Ariel GustavoHeredia, ValeriaBeltramo, Dante MiguelCANCER DRUGSDRUG DELIVERYHYDROPHOBIC INTERACTIONSNANO-DOMAINShttps://purl.org/becyt/ford/2.10https://purl.org/becyt/ford/2Doxorubicin (Dox) is an anthracycline anticancer drug with high water solubility, whose use is limited primarily due to significant side effects. In this study it is shown that Dox interacts with monosialoglycosphingolipid (GM1) ganglioside micelles primarily through hydro-phobic interactions independent of pH and ionic strength. In addition, Dox can be incorporated even into GM1 micelles already containing highly hydrophobic paclitaxel (Ptx). However, it was not possible to incorporate Ptx into Dox-containing GM1 micelles, suggesting that Dox could be occupying a more external position in the micelles. This result is in agreement with a higher hydrolysis of Dox than of Ptx when micelles were incubated at alkaline pH. The loading of Dox into GM1 micelles was observed over a broad range of temperature (4°C–55°C). Furthermore, Dox-loaded micelles were stable in aqueous solutions exhibiting no aggregation or precipitation for up to 2 months when kept at 4°C–25°C and even after freeze–thawing cycles. Upon exposure to blood components, Dox-containing micelles were observed to interact with human serum albumin. However, the amount of human serum albumin that ended up being associated to the micelles was inversely related to the amount of Dox, suggesting that both could share their binding sites. In vitro studies on Hep2 cells showed that the cellular uptake and cytotoxic activity of Dox and Ptx from the micellar complexes were similar to those of the free form of these drugs, even when the micelle was covered with albumin. These results support the idea of the existence of different nano-domains in a single micelle and the fact that this micellar model could be used as a platform for loading and delivering hydrophobic and hydrophilic active pharmaceutical ingredients.Fil: Leonhard, Victoria. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia En Productos y Procesos de Córdoba. Laboratorio de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Alasino, Roxana Valeria. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia En Productos y Procesos de Córdoba. Laboratorio de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Bianco, Ismael Dario. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia En Productos y Procesos de Córdoba. Laboratorio de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Nacional de La Rioja; ArgentinaFil: Garro, Ariel Gustavo. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia En Productos y Procesos de Córdoba. Laboratorio de Biotecnología; ArgentinaFil: Heredia, Valeria. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia En Productos y Procesos de Córdoba. Laboratorio de Biotecnología; ArgentinaFil: Beltramo, Dante Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Católica de Córdoba; Argentina. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia En Productos y Procesos de Córdoba. Laboratorio de Biotecnología; ArgentinaDove Press2015-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/180204Leonhard, Victoria; Alasino, Roxana Valeria; Bianco, Ismael Dario; Garro, Ariel Gustavo; Heredia, Valeria; et al.; Biochemical characterization of the interactions between doxorubicin and lipidic GM1 micelles with or without paclitaxel loading; Dove Press; International Journal of Nanomedicine; 10; 5-2015; 3377-33881176-91141178-2013CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.dovepress.com/international-journal-of-nanomedicine-journalinfo:eu-repo/semantics/altIdentifier/doi/10.2147/IJN.S77153info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:38:35Zoai:ri.conicet.gov.ar:11336/180204instacron: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 10:38:35.458CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Biochemical characterization of the interactions between doxorubicin and lipidic GM1 micelles with or without paclitaxel loading
title Biochemical characterization of the interactions between doxorubicin and lipidic GM1 micelles with or without paclitaxel loading
spellingShingle Biochemical characterization of the interactions between doxorubicin and lipidic GM1 micelles with or without paclitaxel loading
Leonhard, Victoria
CANCER DRUGS
DRUG DELIVERY
HYDROPHOBIC INTERACTIONS
NANO-DOMAINS
title_short Biochemical characterization of the interactions between doxorubicin and lipidic GM1 micelles with or without paclitaxel loading
title_full Biochemical characterization of the interactions between doxorubicin and lipidic GM1 micelles with or without paclitaxel loading
title_fullStr Biochemical characterization of the interactions between doxorubicin and lipidic GM1 micelles with or without paclitaxel loading
title_full_unstemmed Biochemical characterization of the interactions between doxorubicin and lipidic GM1 micelles with or without paclitaxel loading
title_sort Biochemical characterization of the interactions between doxorubicin and lipidic GM1 micelles with or without paclitaxel loading
dc.creator.none.fl_str_mv Leonhard, Victoria
Alasino, Roxana Valeria
Bianco, Ismael Dario
Garro, Ariel Gustavo
Heredia, Valeria
Beltramo, Dante Miguel
author Leonhard, Victoria
author_facet Leonhard, Victoria
Alasino, Roxana Valeria
Bianco, Ismael Dario
Garro, Ariel Gustavo
Heredia, Valeria
Beltramo, Dante Miguel
author_role author
author2 Alasino, Roxana Valeria
Bianco, Ismael Dario
Garro, Ariel Gustavo
Heredia, Valeria
Beltramo, Dante Miguel
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv CANCER DRUGS
DRUG DELIVERY
HYDROPHOBIC INTERACTIONS
NANO-DOMAINS
topic CANCER DRUGS
DRUG DELIVERY
HYDROPHOBIC INTERACTIONS
NANO-DOMAINS
purl_subject.fl_str_mv https://purl.org/becyt/ford/2.10
https://purl.org/becyt/ford/2
dc.description.none.fl_txt_mv Doxorubicin (Dox) is an anthracycline anticancer drug with high water solubility, whose use is limited primarily due to significant side effects. In this study it is shown that Dox interacts with monosialoglycosphingolipid (GM1) ganglioside micelles primarily through hydro-phobic interactions independent of pH and ionic strength. In addition, Dox can be incorporated even into GM1 micelles already containing highly hydrophobic paclitaxel (Ptx). However, it was not possible to incorporate Ptx into Dox-containing GM1 micelles, suggesting that Dox could be occupying a more external position in the micelles. This result is in agreement with a higher hydrolysis of Dox than of Ptx when micelles were incubated at alkaline pH. The loading of Dox into GM1 micelles was observed over a broad range of temperature (4°C–55°C). Furthermore, Dox-loaded micelles were stable in aqueous solutions exhibiting no aggregation or precipitation for up to 2 months when kept at 4°C–25°C and even after freeze–thawing cycles. Upon exposure to blood components, Dox-containing micelles were observed to interact with human serum albumin. However, the amount of human serum albumin that ended up being associated to the micelles was inversely related to the amount of Dox, suggesting that both could share their binding sites. In vitro studies on Hep2 cells showed that the cellular uptake and cytotoxic activity of Dox and Ptx from the micellar complexes were similar to those of the free form of these drugs, even when the micelle was covered with albumin. These results support the idea of the existence of different nano-domains in a single micelle and the fact that this micellar model could be used as a platform for loading and delivering hydrophobic and hydrophilic active pharmaceutical ingredients.
Fil: Leonhard, Victoria. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia En Productos y Procesos de Córdoba. Laboratorio de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina
Fil: Alasino, Roxana Valeria. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia En Productos y Procesos de Córdoba. Laboratorio de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina
Fil: Bianco, Ismael Dario. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia En Productos y Procesos de Córdoba. Laboratorio de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Nacional de La Rioja; Argentina
Fil: Garro, Ariel Gustavo. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia En Productos y Procesos de Córdoba. Laboratorio de Biotecnología; Argentina
Fil: Heredia, Valeria. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia En Productos y Procesos de Córdoba. Laboratorio de Biotecnología; Argentina
Fil: Beltramo, Dante Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Católica de Córdoba; Argentina. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia En Productos y Procesos de Córdoba. Laboratorio de Biotecnología; Argentina
description Doxorubicin (Dox) is an anthracycline anticancer drug with high water solubility, whose use is limited primarily due to significant side effects. In this study it is shown that Dox interacts with monosialoglycosphingolipid (GM1) ganglioside micelles primarily through hydro-phobic interactions independent of pH and ionic strength. In addition, Dox can be incorporated even into GM1 micelles already containing highly hydrophobic paclitaxel (Ptx). However, it was not possible to incorporate Ptx into Dox-containing GM1 micelles, suggesting that Dox could be occupying a more external position in the micelles. This result is in agreement with a higher hydrolysis of Dox than of Ptx when micelles were incubated at alkaline pH. The loading of Dox into GM1 micelles was observed over a broad range of temperature (4°C–55°C). Furthermore, Dox-loaded micelles were stable in aqueous solutions exhibiting no aggregation or precipitation for up to 2 months when kept at 4°C–25°C and even after freeze–thawing cycles. Upon exposure to blood components, Dox-containing micelles were observed to interact with human serum albumin. However, the amount of human serum albumin that ended up being associated to the micelles was inversely related to the amount of Dox, suggesting that both could share their binding sites. In vitro studies on Hep2 cells showed that the cellular uptake and cytotoxic activity of Dox and Ptx from the micellar complexes were similar to those of the free form of these drugs, even when the micelle was covered with albumin. These results support the idea of the existence of different nano-domains in a single micelle and the fact that this micellar model could be used as a platform for loading and delivering hydrophobic and hydrophilic active pharmaceutical ingredients.
publishDate 2015
dc.date.none.fl_str_mv 2015-05
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/11336/180204
Leonhard, Victoria; Alasino, Roxana Valeria; Bianco, Ismael Dario; Garro, Ariel Gustavo; Heredia, Valeria; et al.; Biochemical characterization of the interactions between doxorubicin and lipidic GM1 micelles with or without paclitaxel loading; Dove Press; International Journal of Nanomedicine; 10; 5-2015; 3377-3388
1176-9114
1178-2013
CONICET Digital
CONICET
url http://hdl.handle.net/11336/180204
identifier_str_mv Leonhard, Victoria; Alasino, Roxana Valeria; Bianco, Ismael Dario; Garro, Ariel Gustavo; Heredia, Valeria; et al.; Biochemical characterization of the interactions between doxorubicin and lipidic GM1 micelles with or without paclitaxel loading; Dove Press; International Journal of Nanomedicine; 10; 5-2015; 3377-3388
1176-9114
1178-2013
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://www.dovepress.com/international-journal-of-nanomedicine-journal
info:eu-repo/semantics/altIdentifier/doi/10.2147/IJN.S77153
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
dc.publisher.none.fl_str_mv Dove Press
publisher.none.fl_str_mv Dove Press
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 13.070432

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