Inhibition of P-glycoprotein pumps by PEO–PPO amphiphiles: branched versus linear derivatives

Autores
Alvarez Lorenzo, Carmen; Rey Rico, Ana; Brea, José; Loza, Maria Isabel; Concheiro, Ángel; Sosnik, Alejandro Dario
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Inhibition of the activity of efflux transporters may relevantly improve the chemotherapy of cancer and infectious diseases. Aim: To explore the ability of poloxamines (Tetronic®, X-shaped structure with a central ethylendiamine group and four branches of poly[ethylene oxide]–poly[propylene oxide] [PEO–PPO]) to inhibit the activity of P-glycoprotein (P-gp) on Caco-2 cell monolayers and to elucidate the incidence of the molecular architecture of PEO–PPO block copolymers on the intracellular accumulation of a relevant substrate, doxorubicin, by comparison with poloxamers (Pluronic®, linear triblock copolymers), well-known inhibitors of this efflux transporter. Methods: Both pristine and N-methylated poloxamines displaying a wide range of molecular weights and EO/PO ratios were tested regarding cytocompatibility and accumulation of doxorubicin in Caco-2 monolayers. Verapamil was used as a control. Results: The most active anti-P-gp poloxamines (which enhanced two- to three-fold doxorubicin accumulation compared with verapamil) resulted to be pristine medium-to-high hydrophobic T304, T904, T1301, T901 and T150R1. A notable dependence of the anti-P-gp activity on the copolymer concentration was found. A joint diagram of the inhibitory activity of poloxamers and poloxamines as a function of the effective length of the PPO block is proposed. Conclusion: The anti-P-gp activity is maxima for block copolymers possessing a low-to-medium hydrophilic–lipophilic balance and an ‘effective number’ of PO units ranging from 30 to 50.
Fil: Alvarez Lorenzo, Carmen. Universidad de Santiago de Compostela; España
Fil: Rey Rico, Ana. Universidad de Santiago de Compostela; España
Fil: Brea, José. Universidad de Santiago de Compostela; España
Fil: Loza, Maria Isabel. Universidad de Santiago de Compostela; España
Fil: Concheiro, Ángel. Universidad de Santiago de Compostela; España
Fil: Sosnik, Alejandro Dario. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina
Materia
Cancer
Doxorubicin
Drug Efflux
P-Glycoprotein Inhibition
Poloxamer
Poloxamine
Polymeric Micelle
Transport
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:11336/14453
Acceder
id CONICETDig_cc66d709e6fa0ad8a9ebed046c3d460f
oai_identifier_str oai:ri.conicet.gov.ar:11336/14453
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Inhibition of P-glycoprotein pumps by PEO–PPO amphiphiles: branched versus linear derivativesAlvarez Lorenzo, CarmenRey Rico, AnaBrea, JoséLoza, Maria IsabelConcheiro, ÁngelSosnik, Alejandro DarioCancerDoxorubicinDrug EffluxP-Glycoprotein InhibitionPoloxamerPoloxaminePolymeric MicelleTransporthttps://purl.org/becyt/ford/2.10https://purl.org/becyt/ford/2Inhibition of the activity of efflux transporters may relevantly improve the chemotherapy of cancer and infectious diseases. Aim: To explore the ability of poloxamines (Tetronic®, X-shaped structure with a central ethylendiamine group and four branches of poly[ethylene oxide]–poly[propylene oxide] [PEO–PPO]) to inhibit the activity of P-glycoprotein (P-gp) on Caco-2 cell monolayers and to elucidate the incidence of the molecular architecture of PEO–PPO block copolymers on the intracellular accumulation of a relevant substrate, doxorubicin, by comparison with poloxamers (Pluronic®, linear triblock copolymers), well-known inhibitors of this efflux transporter. Methods: Both pristine and N-methylated poloxamines displaying a wide range of molecular weights and EO/PO ratios were tested regarding cytocompatibility and accumulation of doxorubicin in Caco-2 monolayers. Verapamil was used as a control. Results: The most active anti-P-gp poloxamines (which enhanced two- to three-fold doxorubicin accumulation compared with verapamil) resulted to be pristine medium-to-high hydrophobic T304, T904, T1301, T901 and T150R1. A notable dependence of the anti-P-gp activity on the copolymer concentration was found. A joint diagram of the inhibitory activity of poloxamers and poloxamines as a function of the effective length of the PPO block is proposed. Conclusion: The anti-P-gp activity is maxima for block copolymers possessing a low-to-medium hydrophilic–lipophilic balance and an ‘effective number’ of PO units ranging from 30 to 50.Fil: Alvarez Lorenzo, Carmen. Universidad de Santiago de Compostela; EspañaFil: Rey Rico, Ana. Universidad de Santiago de Compostela; EspañaFil: Brea, José. Universidad de Santiago de Compostela; EspañaFil: Loza, Maria Isabel. Universidad de Santiago de Compostela; EspañaFil: Concheiro, Ángel. Universidad de Santiago de Compostela; EspañaFil: Sosnik, Alejandro Dario. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; ArgentinaFuture Medicine2010-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/14453Alvarez Lorenzo, Carmen; Rey Rico, Ana; Brea, José; Loza, Maria Isabel; Concheiro, Ángel; et al.; Inhibition of P-glycoprotein pumps by PEO–PPO amphiphiles: branched versus linear derivatives; Future Medicine; Nanomedicine; 5; 9; 12-2010; 1371-13831743-5889enginfo:eu-repo/semantics/altIdentifier/url/http://www.futuremedicine.com/doi/full/10.2217/nnm.10.53info:eu-repo/semantics/altIdentifier/doi/10.2217/nnm.10.53info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:22:51Zoai:ri.conicet.gov.ar:11336/14453instacron: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:34982025-10-15 15:22:52.215CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Inhibition of P-glycoprotein pumps by PEO–PPO amphiphiles: branched versus linear derivatives
title Inhibition of P-glycoprotein pumps by PEO–PPO amphiphiles: branched versus linear derivatives
spellingShingle Inhibition of P-glycoprotein pumps by PEO–PPO amphiphiles: branched versus linear derivatives
Alvarez Lorenzo, Carmen
Cancer
Doxorubicin
Drug Efflux
P-Glycoprotein Inhibition
Poloxamer
Poloxamine
Polymeric Micelle
Transport
title_short Inhibition of P-glycoprotein pumps by PEO–PPO amphiphiles: branched versus linear derivatives
title_full Inhibition of P-glycoprotein pumps by PEO–PPO amphiphiles: branched versus linear derivatives
title_fullStr Inhibition of P-glycoprotein pumps by PEO–PPO amphiphiles: branched versus linear derivatives
title_full_unstemmed Inhibition of P-glycoprotein pumps by PEO–PPO amphiphiles: branched versus linear derivatives
title_sort Inhibition of P-glycoprotein pumps by PEO–PPO amphiphiles: branched versus linear derivatives
dc.creator.none.fl_str_mv Alvarez Lorenzo, Carmen
Rey Rico, Ana
Brea, José
Loza, Maria Isabel
Concheiro, Ángel
Sosnik, Alejandro Dario
author Alvarez Lorenzo, Carmen
author_facet Alvarez Lorenzo, Carmen
Rey Rico, Ana
Brea, José
Loza, Maria Isabel
Concheiro, Ángel
Sosnik, Alejandro Dario
author_role author
author2 Rey Rico, Ana
Brea, José
Loza, Maria Isabel
Concheiro, Ángel
Sosnik, Alejandro Dario
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Cancer
Doxorubicin
Drug Efflux
P-Glycoprotein Inhibition
Poloxamer
Poloxamine
Polymeric Micelle
Transport
topic Cancer
Doxorubicin
Drug Efflux
P-Glycoprotein Inhibition
Poloxamer
Poloxamine
Polymeric Micelle
Transport
purl_subject.fl_str_mv https://purl.org/becyt/ford/2.10
https://purl.org/becyt/ford/2
dc.description.none.fl_txt_mv Inhibition of the activity of efflux transporters may relevantly improve the chemotherapy of cancer and infectious diseases. Aim: To explore the ability of poloxamines (Tetronic®, X-shaped structure with a central ethylendiamine group and four branches of poly[ethylene oxide]–poly[propylene oxide] [PEO–PPO]) to inhibit the activity of P-glycoprotein (P-gp) on Caco-2 cell monolayers and to elucidate the incidence of the molecular architecture of PEO–PPO block copolymers on the intracellular accumulation of a relevant substrate, doxorubicin, by comparison with poloxamers (Pluronic®, linear triblock copolymers), well-known inhibitors of this efflux transporter. Methods: Both pristine and N-methylated poloxamines displaying a wide range of molecular weights and EO/PO ratios were tested regarding cytocompatibility and accumulation of doxorubicin in Caco-2 monolayers. Verapamil was used as a control. Results: The most active anti-P-gp poloxamines (which enhanced two- to three-fold doxorubicin accumulation compared with verapamil) resulted to be pristine medium-to-high hydrophobic T304, T904, T1301, T901 and T150R1. A notable dependence of the anti-P-gp activity on the copolymer concentration was found. A joint diagram of the inhibitory activity of poloxamers and poloxamines as a function of the effective length of the PPO block is proposed. Conclusion: The anti-P-gp activity is maxima for block copolymers possessing a low-to-medium hydrophilic–lipophilic balance and an ‘effective number’ of PO units ranging from 30 to 50.
Fil: Alvarez Lorenzo, Carmen. Universidad de Santiago de Compostela; España
Fil: Rey Rico, Ana. Universidad de Santiago de Compostela; España
Fil: Brea, José. Universidad de Santiago de Compostela; España
Fil: Loza, Maria Isabel. Universidad de Santiago de Compostela; España
Fil: Concheiro, Ángel. Universidad de Santiago de Compostela; España
Fil: Sosnik, Alejandro Dario. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina
description Inhibition of the activity of efflux transporters may relevantly improve the chemotherapy of cancer and infectious diseases. Aim: To explore the ability of poloxamines (Tetronic®, X-shaped structure with a central ethylendiamine group and four branches of poly[ethylene oxide]–poly[propylene oxide] [PEO–PPO]) to inhibit the activity of P-glycoprotein (P-gp) on Caco-2 cell monolayers and to elucidate the incidence of the molecular architecture of PEO–PPO block copolymers on the intracellular accumulation of a relevant substrate, doxorubicin, by comparison with poloxamers (Pluronic®, linear triblock copolymers), well-known inhibitors of this efflux transporter. Methods: Both pristine and N-methylated poloxamines displaying a wide range of molecular weights and EO/PO ratios were tested regarding cytocompatibility and accumulation of doxorubicin in Caco-2 monolayers. Verapamil was used as a control. Results: The most active anti-P-gp poloxamines (which enhanced two- to three-fold doxorubicin accumulation compared with verapamil) resulted to be pristine medium-to-high hydrophobic T304, T904, T1301, T901 and T150R1. A notable dependence of the anti-P-gp activity on the copolymer concentration was found. A joint diagram of the inhibitory activity of poloxamers and poloxamines as a function of the effective length of the PPO block is proposed. Conclusion: The anti-P-gp activity is maxima for block copolymers possessing a low-to-medium hydrophilic–lipophilic balance and an ‘effective number’ of PO units ranging from 30 to 50.
publishDate 2010
dc.date.none.fl_str_mv 2010-12
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/11336/14453
Alvarez Lorenzo, Carmen; Rey Rico, Ana; Brea, José; Loza, Maria Isabel; Concheiro, Ángel; et al.; Inhibition of P-glycoprotein pumps by PEO–PPO amphiphiles: branched versus linear derivatives; Future Medicine; Nanomedicine; 5; 9; 12-2010; 1371-1383
1743-5889
url http://hdl.handle.net/11336/14453
identifier_str_mv Alvarez Lorenzo, Carmen; Rey Rico, Ana; Brea, José; Loza, Maria Isabel; Concheiro, Ángel; et al.; Inhibition of P-glycoprotein pumps by PEO–PPO amphiphiles: branched versus linear derivatives; Future Medicine; Nanomedicine; 5; 9; 12-2010; 1371-1383
1743-5889
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.futuremedicine.com/doi/full/10.2217/nnm.10.53
info:eu-repo/semantics/altIdentifier/doi/10.2217/nnm.10.53
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
dc.publisher.none.fl_str_mv Future Medicine
publisher.none.fl_str_mv Future Medicine
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_ 1846083375795798016
score 13.22299

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