Reversible exposure of hydrophobic residues on albumin as a novel strategy for formulation of nanodelivery vehicles for taxanes

Autores
Garro, Ariel Gustavo; Beltramo, Dante Miguel; Alasino, Roxana Valeria; Leonhard, Victoria; Heredia, Valeria; Bianco, Ismael Dario
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
We report herein a novel strategy for the preparation of protein-based nanodelivery vehicles for hydrophobic active pharmaceutical ingredients. The procedure consisted of three steps, ie, exposure of hydrophobic residues of a protein to a pH-induced partial unfolding: interaction between hydrophobic residues on the protein and the hydrophobic active pharmaceutical ingredient, and a final step where the structure of the protein was reversed to a native-like state by returning to neutral pH. As proof of concept, the interaction of paclitaxel with partially unfolded states of human serum albumin was evaluated as a potential method for the preparation of water-soluble complexes of the taxane with albumin. We found that paclitaxel readily binds to pH-induced partially unfolded albumin, leading to the formation of optically clear water-soluble complexes. The complexes thus formed were more stable in solution when the albumin native state was at least partially restored by neutralization of the solution to a pH around 7. It was also observed that the hydrodynamic radius of human serum albumin was only slightly increased after the cycle of pH changes, remaining in a monomeric state with a size according to paclitaxel binding. Furthermore, paclitaxel binding did not affect the overall exposure of charged groups of human serum albumin, as evaluated by its interaction with an ionic exchange resin. The in vitro biological activity of the complexes formed was qualitatively equivalent to that of a Cremophor®-based formulation.
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: Beltramo, Dante Miguel. 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. 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: 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: Heredia, Valeria. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia En Productos y Procesos de Córdoba. Laboratorio de Biotecnología; Argentina
Fil: Bianco, Ismael Dario. Universidad Nacional de La Rioja; Argentina. 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
Materia
HUMAN SERUM ALBUMIN
PACLITAXEL
UNFOLDED STATES
SOLUBILITY
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:11336/192725
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/192725
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Reversible exposure of hydrophobic residues on albumin as a novel strategy for formulation of nanodelivery vehicles for taxanesGarro, Ariel GustavoBeltramo, Dante MiguelAlasino, Roxana ValeriaLeonhard, VictoriaHeredia, ValeriaBianco, Ismael DarioHUMAN SERUM ALBUMINPACLITAXELUNFOLDED STATESSOLUBILITYhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1We report herein a novel strategy for the preparation of protein-based nanodelivery vehicles for hydrophobic active pharmaceutical ingredients. The procedure consisted of three steps, ie, exposure of hydrophobic residues of a protein to a pH-induced partial unfolding: interaction between hydrophobic residues on the protein and the hydrophobic active pharmaceutical ingredient, and a final step where the structure of the protein was reversed to a native-like state by returning to neutral pH. As proof of concept, the interaction of paclitaxel with partially unfolded states of human serum albumin was evaluated as a potential method for the preparation of water-soluble complexes of the taxane with albumin. We found that paclitaxel readily binds to pH-induced partially unfolded albumin, leading to the formation of optically clear water-soluble complexes. The complexes thus formed were more stable in solution when the albumin native state was at least partially restored by neutralization of the solution to a pH around 7. It was also observed that the hydrodynamic radius of human serum albumin was only slightly increased after the cycle of pH changes, remaining in a monomeric state with a size according to paclitaxel binding. Furthermore, paclitaxel binding did not affect the overall exposure of charged groups of human serum albumin, as evaluated by its interaction with an ionic exchange resin. The in vitro biological activity of the complexes formed was qualitatively equivalent to that of a Cremophor®-based formulation.Fil: Garro, Ariel Gustavo. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia En Productos y Procesos de Córdoba. Laboratorio de Biotecnología; ArgentinaFil: Beltramo, Dante Miguel. 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. 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: 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: Heredia, Valeria. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia En Productos y Procesos de Córdoba. Laboratorio de Biotecnología; ArgentinaFil: Bianco, Ismael Dario. Universidad Nacional de La Rioja; Argentina. 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; ArgentinaDove Press2011-06info: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/11336/192725Garro, Ariel Gustavo; Beltramo, Dante Miguel; Alasino, Roxana Valeria; Leonhard, Victoria; Heredia, Valeria; et al.; Reversible exposure of hydrophobic residues on albumin as a novel strategy for formulation of nanodelivery vehicles for taxanes; Dove Press; International Journal of Nanomedicine; 6; 6-2011; 1193-12001176-91141178-2013CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.2147/IJN.S19163info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:09:26Zoai:ri.conicet.gov.ar:11336/192725instacron: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 10:09:27.144CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Reversible exposure of hydrophobic residues on albumin as a novel strategy for formulation of nanodelivery vehicles for taxanes
title Reversible exposure of hydrophobic residues on albumin as a novel strategy for formulation of nanodelivery vehicles for taxanes
spellingShingle Reversible exposure of hydrophobic residues on albumin as a novel strategy for formulation of nanodelivery vehicles for taxanes
Garro, Ariel Gustavo
HUMAN SERUM ALBUMIN
PACLITAXEL
UNFOLDED STATES
SOLUBILITY
title_short Reversible exposure of hydrophobic residues on albumin as a novel strategy for formulation of nanodelivery vehicles for taxanes
title_full Reversible exposure of hydrophobic residues on albumin as a novel strategy for formulation of nanodelivery vehicles for taxanes
title_fullStr Reversible exposure of hydrophobic residues on albumin as a novel strategy for formulation of nanodelivery vehicles for taxanes
title_full_unstemmed Reversible exposure of hydrophobic residues on albumin as a novel strategy for formulation of nanodelivery vehicles for taxanes
title_sort Reversible exposure of hydrophobic residues on albumin as a novel strategy for formulation of nanodelivery vehicles for taxanes
dc.creator.none.fl_str_mv Garro, Ariel Gustavo
Beltramo, Dante Miguel
Alasino, Roxana Valeria
Leonhard, Victoria
Heredia, Valeria
Bianco, Ismael Dario
author Garro, Ariel Gustavo
author_facet Garro, Ariel Gustavo
Beltramo, Dante Miguel
Alasino, Roxana Valeria
Leonhard, Victoria
Heredia, Valeria
Bianco, Ismael Dario
author_role author
author2 Beltramo, Dante Miguel
Alasino, Roxana Valeria
Leonhard, Victoria
Heredia, Valeria
Bianco, Ismael Dario
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv HUMAN SERUM ALBUMIN
PACLITAXEL
UNFOLDED STATES
SOLUBILITY
topic HUMAN SERUM ALBUMIN
PACLITAXEL
UNFOLDED STATES
SOLUBILITY
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv We report herein a novel strategy for the preparation of protein-based nanodelivery vehicles for hydrophobic active pharmaceutical ingredients. The procedure consisted of three steps, ie, exposure of hydrophobic residues of a protein to a pH-induced partial unfolding: interaction between hydrophobic residues on the protein and the hydrophobic active pharmaceutical ingredient, and a final step where the structure of the protein was reversed to a native-like state by returning to neutral pH. As proof of concept, the interaction of paclitaxel with partially unfolded states of human serum albumin was evaluated as a potential method for the preparation of water-soluble complexes of the taxane with albumin. We found that paclitaxel readily binds to pH-induced partially unfolded albumin, leading to the formation of optically clear water-soluble complexes. The complexes thus formed were more stable in solution when the albumin native state was at least partially restored by neutralization of the solution to a pH around 7. It was also observed that the hydrodynamic radius of human serum albumin was only slightly increased after the cycle of pH changes, remaining in a monomeric state with a size according to paclitaxel binding. Furthermore, paclitaxel binding did not affect the overall exposure of charged groups of human serum albumin, as evaluated by its interaction with an ionic exchange resin. The in vitro biological activity of the complexes formed was qualitatively equivalent to that of a Cremophor®-based formulation.
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: Beltramo, Dante Miguel. 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. 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: 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: Heredia, Valeria. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia En Productos y Procesos de Córdoba. Laboratorio de Biotecnología; Argentina
Fil: Bianco, Ismael Dario. Universidad Nacional de La Rioja; Argentina. 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
description We report herein a novel strategy for the preparation of protein-based nanodelivery vehicles for hydrophobic active pharmaceutical ingredients. The procedure consisted of three steps, ie, exposure of hydrophobic residues of a protein to a pH-induced partial unfolding: interaction between hydrophobic residues on the protein and the hydrophobic active pharmaceutical ingredient, and a final step where the structure of the protein was reversed to a native-like state by returning to neutral pH. As proof of concept, the interaction of paclitaxel with partially unfolded states of human serum albumin was evaluated as a potential method for the preparation of water-soluble complexes of the taxane with albumin. We found that paclitaxel readily binds to pH-induced partially unfolded albumin, leading to the formation of optically clear water-soluble complexes. The complexes thus formed were more stable in solution when the albumin native state was at least partially restored by neutralization of the solution to a pH around 7. It was also observed that the hydrodynamic radius of human serum albumin was only slightly increased after the cycle of pH changes, remaining in a monomeric state with a size according to paclitaxel binding. Furthermore, paclitaxel binding did not affect the overall exposure of charged groups of human serum albumin, as evaluated by its interaction with an ionic exchange resin. The in vitro biological activity of the complexes formed was qualitatively equivalent to that of a Cremophor®-based formulation.
publishDate 2011
dc.date.none.fl_str_mv 2011-06
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/11336/192725
Garro, Ariel Gustavo; Beltramo, Dante Miguel; Alasino, Roxana Valeria; Leonhard, Victoria; Heredia, Valeria; et al.; Reversible exposure of hydrophobic residues on albumin as a novel strategy for formulation of nanodelivery vehicles for taxanes; Dove Press; International Journal of Nanomedicine; 6; 6-2011; 1193-1200
1176-9114
1178-2013
CONICET Digital
CONICET
url http://hdl.handle.net/11336/192725
identifier_str_mv Garro, Ariel Gustavo; Beltramo, Dante Miguel; Alasino, Roxana Valeria; Leonhard, Victoria; Heredia, Valeria; et al.; Reversible exposure of hydrophobic residues on albumin as a novel strategy for formulation of nanodelivery vehicles for taxanes; Dove Press; International Journal of Nanomedicine; 6; 6-2011; 1193-1200
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/doi/10.2147/IJN.S19163
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 13.13397

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