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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/14453
Ver los metadatos del registro completo
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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 Técnicas2025-09-29T10:25:43Zoai: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:34982025-09-29 10:25:44.178CONICET 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 |
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1844614256572497920 |
score |
13.070432 |