N-alkylation of poloxamines modulates micellar assembly and encapsulation and release of the antiretroviral efavirenz

Autores
Chiappetta, Diego Andrés; Alvarez Lorenzo, Carmen; Rey Rico, Ana; Taboada, Pablo; Concheiro, Angel; Sosnik, Alejandro Dario
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Poloxamines (X-shaped poly(ethylene oxide)-poly(propylene oxide) (PEO-PPO) diblocks connected to a central ethylenediamine group) were N-methylated and N-allylated with the aim of widening their versatility as drug nanocarriers. The self-aggregation properties of various derivatives, covering a wide range of molecular weights and EO/PO ratios, were thoroughly investigated. The cytocompatibility of different modified poloxamines was compared to that of the pristine counterparts by MTT and LDH assays. The most hydrophilic varieties were highly cytocompatible even at concentrations of 5%. Toward the optimization of the oral pharmacotherapy of the Human Immunodeficiency Virus (HIV) infection in pediatric patients, the encapsulation and in vitro delivery of efavirenz (EFV), a lipophilic first-line antiretroviral drug, were evaluated. Pristine and N-alkylated poloxamines behaved as highly efficient EFV solubilizers enhancing the aqueous solubility of the drug between 166 and 7426-times. EFV promotes self-micellization of poloxamines; their tiny structural modification (i.e., just one methyl- or allyl-group) being able to regulate drug/micellar core interaction. Despite the physical stability of the micelles against dilution in physiological mimicking fluids, the N-alkylated derivatives were slightly more prone to disassembly promoting EFV release from the micellar reservoir. For all the derivatives evaluated, the in vitro release fitted zero-order kinetics and was sustained for at least 24. h. These findings point out N-alkylated poloxamines as promising nanocarriers for oral or parenteral drug delivery.
Fil: Chiappetta, Diego Andrés. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Alvarez Lorenzo, Carmen. Universidad de Santiago de Compostela; España
Fil: Rey Rico, Ana. Universidad de Santiago de Compostela; España
Fil: Taboada, Pablo. Universidad de Santiago de Compostela; España
Fil: Concheiro, Angel. Universidad de Santiago de Compostela; España
Fil: Sosnik, Alejandro Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina
Materia
DRUG RELEASE
EFAVIRENZ ENCAPSULATION
HIV/AIDS
POLYMERIC MICELLES
PRISTINE AND N-ALKYLATED POLOXAMINES SELF-ASSEMBLY
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:11336/112988
Acceder
id CONICETDig_21b30712679d689e83390ce840359d76
oai_identifier_str oai:ri.conicet.gov.ar:11336/112988
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling N-alkylation of poloxamines modulates micellar assembly and encapsulation and release of the antiretroviral efavirenzChiappetta, Diego AndrésAlvarez Lorenzo, CarmenRey Rico, AnaTaboada, PabloConcheiro, AngelSosnik, Alejandro DarioDRUG RELEASEEFAVIRENZ ENCAPSULATIONHIV/AIDSPOLYMERIC MICELLESPRISTINE AND N-ALKYLATED POLOXAMINES SELF-ASSEMBLYhttps://purl.org/becyt/ford/2.10https://purl.org/becyt/ford/2Poloxamines (X-shaped poly(ethylene oxide)-poly(propylene oxide) (PEO-PPO) diblocks connected to a central ethylenediamine group) were N-methylated and N-allylated with the aim of widening their versatility as drug nanocarriers. The self-aggregation properties of various derivatives, covering a wide range of molecular weights and EO/PO ratios, were thoroughly investigated. The cytocompatibility of different modified poloxamines was compared to that of the pristine counterparts by MTT and LDH assays. The most hydrophilic varieties were highly cytocompatible even at concentrations of 5%. Toward the optimization of the oral pharmacotherapy of the Human Immunodeficiency Virus (HIV) infection in pediatric patients, the encapsulation and in vitro delivery of efavirenz (EFV), a lipophilic first-line antiretroviral drug, were evaluated. Pristine and N-alkylated poloxamines behaved as highly efficient EFV solubilizers enhancing the aqueous solubility of the drug between 166 and 7426-times. EFV promotes self-micellization of poloxamines; their tiny structural modification (i.e., just one methyl- or allyl-group) being able to regulate drug/micellar core interaction. Despite the physical stability of the micelles against dilution in physiological mimicking fluids, the N-alkylated derivatives were slightly more prone to disassembly promoting EFV release from the micellar reservoir. For all the derivatives evaluated, the in vitro release fitted zero-order kinetics and was sustained for at least 24. h. These findings point out N-alkylated poloxamines as promising nanocarriers for oral or parenteral drug delivery.Fil: Chiappetta, Diego Andrés. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Alvarez Lorenzo, Carmen. Universidad de Santiago de Compostela; EspañaFil: Rey Rico, Ana. Universidad de Santiago de Compostela; EspañaFil: Taboada, Pablo. Universidad de Santiago de Compostela; EspañaFil: Concheiro, Angel. Universidad de Santiago de Compostela; EspañaFil: Sosnik, Alejandro Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; ArgentinaElsevier Science2010-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/112988Chiappetta, Diego Andrés; Alvarez Lorenzo, Carmen; Rey Rico, Ana; Taboada, Pablo; Concheiro, Angel; et al.; N-alkylation of poloxamines modulates micellar assembly and encapsulation and release of the antiretroviral efavirenz; Elsevier Science; European Journal Of Pharmaceutics And Biopharmaceutics; 76; 1; 9-2010; 24-370939-6411CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0939641110001438info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejpb.2010.05.007info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-17T10:47:29Zoai:ri.conicet.gov.ar:11336/112988instacron: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:34982025-09-17 10:47:29.281CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv N-alkylation of poloxamines modulates micellar assembly and encapsulation and release of the antiretroviral efavirenz
title N-alkylation of poloxamines modulates micellar assembly and encapsulation and release of the antiretroviral efavirenz
spellingShingle N-alkylation of poloxamines modulates micellar assembly and encapsulation and release of the antiretroviral efavirenz
Chiappetta, Diego Andrés
DRUG RELEASE
EFAVIRENZ ENCAPSULATION
HIV/AIDS
POLYMERIC MICELLES
PRISTINE AND N-ALKYLATED POLOXAMINES SELF-ASSEMBLY
title_short N-alkylation of poloxamines modulates micellar assembly and encapsulation and release of the antiretroviral efavirenz
title_full N-alkylation of poloxamines modulates micellar assembly and encapsulation and release of the antiretroviral efavirenz
title_fullStr N-alkylation of poloxamines modulates micellar assembly and encapsulation and release of the antiretroviral efavirenz
title_full_unstemmed N-alkylation of poloxamines modulates micellar assembly and encapsulation and release of the antiretroviral efavirenz
title_sort N-alkylation of poloxamines modulates micellar assembly and encapsulation and release of the antiretroviral efavirenz
dc.creator.none.fl_str_mv Chiappetta, Diego Andrés
Alvarez Lorenzo, Carmen
Rey Rico, Ana
Taboada, Pablo
Concheiro, Angel
Sosnik, Alejandro Dario
author Chiappetta, Diego Andrés
author_facet Chiappetta, Diego Andrés
Alvarez Lorenzo, Carmen
Rey Rico, Ana
Taboada, Pablo
Concheiro, Angel
Sosnik, Alejandro Dario
author_role author
author2 Alvarez Lorenzo, Carmen
Rey Rico, Ana
Taboada, Pablo
Concheiro, Angel
Sosnik, Alejandro Dario
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv DRUG RELEASE
EFAVIRENZ ENCAPSULATION
HIV/AIDS
POLYMERIC MICELLES
PRISTINE AND N-ALKYLATED POLOXAMINES SELF-ASSEMBLY
topic DRUG RELEASE
EFAVIRENZ ENCAPSULATION
HIV/AIDS
POLYMERIC MICELLES
PRISTINE AND N-ALKYLATED POLOXAMINES SELF-ASSEMBLY
purl_subject.fl_str_mv https://purl.org/becyt/ford/2.10
https://purl.org/becyt/ford/2
dc.description.none.fl_txt_mv Poloxamines (X-shaped poly(ethylene oxide)-poly(propylene oxide) (PEO-PPO) diblocks connected to a central ethylenediamine group) were N-methylated and N-allylated with the aim of widening their versatility as drug nanocarriers. The self-aggregation properties of various derivatives, covering a wide range of molecular weights and EO/PO ratios, were thoroughly investigated. The cytocompatibility of different modified poloxamines was compared to that of the pristine counterparts by MTT and LDH assays. The most hydrophilic varieties were highly cytocompatible even at concentrations of 5%. Toward the optimization of the oral pharmacotherapy of the Human Immunodeficiency Virus (HIV) infection in pediatric patients, the encapsulation and in vitro delivery of efavirenz (EFV), a lipophilic first-line antiretroviral drug, were evaluated. Pristine and N-alkylated poloxamines behaved as highly efficient EFV solubilizers enhancing the aqueous solubility of the drug between 166 and 7426-times. EFV promotes self-micellization of poloxamines; their tiny structural modification (i.e., just one methyl- or allyl-group) being able to regulate drug/micellar core interaction. Despite the physical stability of the micelles against dilution in physiological mimicking fluids, the N-alkylated derivatives were slightly more prone to disassembly promoting EFV release from the micellar reservoir. For all the derivatives evaluated, the in vitro release fitted zero-order kinetics and was sustained for at least 24. h. These findings point out N-alkylated poloxamines as promising nanocarriers for oral or parenteral drug delivery.
Fil: Chiappetta, Diego Andrés. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Alvarez Lorenzo, Carmen. Universidad de Santiago de Compostela; España
Fil: Rey Rico, Ana. Universidad de Santiago de Compostela; España
Fil: Taboada, Pablo. Universidad de Santiago de Compostela; España
Fil: Concheiro, Angel. Universidad de Santiago de Compostela; España
Fil: Sosnik, Alejandro Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina
description Poloxamines (X-shaped poly(ethylene oxide)-poly(propylene oxide) (PEO-PPO) diblocks connected to a central ethylenediamine group) were N-methylated and N-allylated with the aim of widening their versatility as drug nanocarriers. The self-aggregation properties of various derivatives, covering a wide range of molecular weights and EO/PO ratios, were thoroughly investigated. The cytocompatibility of different modified poloxamines was compared to that of the pristine counterparts by MTT and LDH assays. The most hydrophilic varieties were highly cytocompatible even at concentrations of 5%. Toward the optimization of the oral pharmacotherapy of the Human Immunodeficiency Virus (HIV) infection in pediatric patients, the encapsulation and in vitro delivery of efavirenz (EFV), a lipophilic first-line antiretroviral drug, were evaluated. Pristine and N-alkylated poloxamines behaved as highly efficient EFV solubilizers enhancing the aqueous solubility of the drug between 166 and 7426-times. EFV promotes self-micellization of poloxamines; their tiny structural modification (i.e., just one methyl- or allyl-group) being able to regulate drug/micellar core interaction. Despite the physical stability of the micelles against dilution in physiological mimicking fluids, the N-alkylated derivatives were slightly more prone to disassembly promoting EFV release from the micellar reservoir. For all the derivatives evaluated, the in vitro release fitted zero-order kinetics and was sustained for at least 24. h. These findings point out N-alkylated poloxamines as promising nanocarriers for oral or parenteral drug delivery.
publishDate 2010
dc.date.none.fl_str_mv 2010-09
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/11336/112988
Chiappetta, Diego Andrés; Alvarez Lorenzo, Carmen; Rey Rico, Ana; Taboada, Pablo; Concheiro, Angel; et al.; N-alkylation of poloxamines modulates micellar assembly and encapsulation and release of the antiretroviral efavirenz; Elsevier Science; European Journal Of Pharmaceutics And Biopharmaceutics; 76; 1; 9-2010; 24-37
0939-6411
CONICET Digital
CONICET
url http://hdl.handle.net/11336/112988
identifier_str_mv Chiappetta, Diego Andrés; Alvarez Lorenzo, Carmen; Rey Rico, Ana; Taboada, Pablo; Concheiro, Angel; et al.; N-alkylation of poloxamines modulates micellar assembly and encapsulation and release of the antiretroviral efavirenz; Elsevier Science; European Journal Of Pharmaceutics And Biopharmaceutics; 76; 1; 9-2010; 24-37
0939-6411
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0939641110001438
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejpb.2010.05.007
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
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_ 1843606060805390336
score 13.001348

Publicaciones similares