Development and Evaluation of 2-Amino-7-Fluorophenazine 5,10-Dioxide Polymeric Micelles as Antitumoral Agents for 4T1 Breast Cancer

Autores
Lecot, Nicole; Dávila Belzunce, María Belén; Sánchez, Carina; Fernández, Marcelo; González, Mercedes; Cabral, Pablo; Cerecetto, Hugo; Glisoni, Romina Julieta
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
2-Amino-7-fluorophenazine 5,10-dioxide (FNZ) is a bioreducible prodrug, poorly soluble in water, with potential anticancer activity on hypoxic-tumors. This poor solubility limits its potential applications in clinic. Amphiphilic pristine polymeric micelles (PMs) based on triblock copolymers Pluronic® and Tetronic®, glycosylated derivatives and their mixtures with preformed-liposomes (LPS), were analyzed as strategies to improve the bioavailability of FNZ. FNZ encapsulations were performed and the obtaining nanostructures were characterized using UV-visible spectroscopy (UV- VIS), Transmission Electron Microscopy (TEM), Fourier transform infrared analysis and Dynamic Light Scattering (DLS). The most promising nanoformulations were analyzed for their potential toxicity and pharmacologically, at 20 mg/kg FNZ-doses, in a stage-IV murine metastatic-breast tumor model. The results revealed that the solubility of the encapsulated-FNZ increased up to seven times and the analysis (UV-VIS, DLS and TEM) confirmed the interaction between vehicles and FNZ. In all the cases appropriate encapsulation efficiencies (up to 70%), monodisperse nanometric particle sizes (PDI = 0.180–0.335), adequate Z-potentials (-1.59 to -26.4 mV), stabilities and spherical morphologies were obtained. The in vitro profile of FNZ controlled releases corresponded mainly to a kinetic Higuchi model. The in vitro/in vivo biological studies revealed non-toxicity and relevant tumor-weight diminution (up to 61%).
Fil: Lecot, Nicole. Universidad de la República; Uruguay
Fil: Dávila Belzunce, María Belén. Universidad de la República; Uruguay
Fil: Sánchez, Carina. Universidad de la República; Uruguay
Fil: Fernández, Marcelo. Universidad de la República; Uruguay
Fil: González, Mercedes. Universidad de la República; Uruguay
Fil: Cabral, Pablo. Universidad de la República; Uruguay
Fil: Cerecetto, Hugo. Universidad de la República; Uruguay
Fil: Glisoni, Romina Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; Argentina
Materia
10-DIOXIDE
4T1-TUMOR MODEL
AMPHIPHILIC PRISTINE POLYMERIC MICELLES
BIOREDUCTIVE-DRUG
IN VIVO ANTITUMORAL ACTIVITY
PHENAZINE-5
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/170609
Acceder
id CONICETDig_b6706542b4ef5c09519f84448b40b711
oai_identifier_str oai:ri.conicet.gov.ar:11336/170609
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Development and Evaluation of 2-Amino-7-Fluorophenazine 5,10-Dioxide Polymeric Micelles as Antitumoral Agents for 4T1 Breast CancerLecot, NicoleDávila Belzunce, María BelénSánchez, CarinaFernández, MarceloGonzález, MercedesCabral, PabloCerecetto, HugoGlisoni, Romina Julieta10-DIOXIDE4T1-TUMOR MODELAMPHIPHILIC PRISTINE POLYMERIC MICELLESBIOREDUCTIVE-DRUGIN VIVO ANTITUMORAL ACTIVITYPHENAZINE-5https://purl.org/becyt/ford/2.10https://purl.org/becyt/ford/22-Amino-7-fluorophenazine 5,10-dioxide (FNZ) is a bioreducible prodrug, poorly soluble in water, with potential anticancer activity on hypoxic-tumors. This poor solubility limits its potential applications in clinic. Amphiphilic pristine polymeric micelles (PMs) based on triblock copolymers Pluronic® and Tetronic®, glycosylated derivatives and their mixtures with preformed-liposomes (LPS), were analyzed as strategies to improve the bioavailability of FNZ. FNZ encapsulations were performed and the obtaining nanostructures were characterized using UV-visible spectroscopy (UV- VIS), Transmission Electron Microscopy (TEM), Fourier transform infrared analysis and Dynamic Light Scattering (DLS). The most promising nanoformulations were analyzed for their potential toxicity and pharmacologically, at 20 mg/kg FNZ-doses, in a stage-IV murine metastatic-breast tumor model. The results revealed that the solubility of the encapsulated-FNZ increased up to seven times and the analysis (UV-VIS, DLS and TEM) confirmed the interaction between vehicles and FNZ. In all the cases appropriate encapsulation efficiencies (up to 70%), monodisperse nanometric particle sizes (PDI = 0.180–0.335), adequate Z-potentials (-1.59 to -26.4 mV), stabilities and spherical morphologies were obtained. The in vitro profile of FNZ controlled releases corresponded mainly to a kinetic Higuchi model. The in vitro/in vivo biological studies revealed non-toxicity and relevant tumor-weight diminution (up to 61%).Fil: Lecot, Nicole. Universidad de la República; UruguayFil: Dávila Belzunce, María Belén. Universidad de la República; UruguayFil: Sánchez, Carina. Universidad de la República; UruguayFil: Fernández, Marcelo. Universidad de la República; UruguayFil: González, Mercedes. Universidad de la República; UruguayFil: Cabral, Pablo. Universidad de la República; UruguayFil: Cerecetto, Hugo. Universidad de la República; UruguayFil: Glisoni, Romina Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; ArgentinaMDPI2021-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/170609Lecot, Nicole; Dávila Belzunce, María Belén; Sánchez, Carina; Fernández, Marcelo; González, Mercedes; et al.; Development and Evaluation of 2-Amino-7-Fluorophenazine 5,10-Dioxide Polymeric Micelles as Antitumoral Agents for 4T1 Breast Cancer; MDPI; Polymers; 14; 1; 1-2021; 1-142073-4360CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2073-4360/14/1/71info:eu-repo/semantics/altIdentifier/doi/10.3390/polym14010071info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:09:59Zoai:ri.conicet.gov.ar:11336/170609instacron: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:34982025-09-10 13:10:00.184CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Development and Evaluation of 2-Amino-7-Fluorophenazine 5,10-Dioxide Polymeric Micelles as Antitumoral Agents for 4T1 Breast Cancer
title Development and Evaluation of 2-Amino-7-Fluorophenazine 5,10-Dioxide Polymeric Micelles as Antitumoral Agents for 4T1 Breast Cancer
spellingShingle Development and Evaluation of 2-Amino-7-Fluorophenazine 5,10-Dioxide Polymeric Micelles as Antitumoral Agents for 4T1 Breast Cancer
Lecot, Nicole
10-DIOXIDE
4T1-TUMOR MODEL
AMPHIPHILIC PRISTINE POLYMERIC MICELLES
BIOREDUCTIVE-DRUG
IN VIVO ANTITUMORAL ACTIVITY
PHENAZINE-5
title_short Development and Evaluation of 2-Amino-7-Fluorophenazine 5,10-Dioxide Polymeric Micelles as Antitumoral Agents for 4T1 Breast Cancer
title_full Development and Evaluation of 2-Amino-7-Fluorophenazine 5,10-Dioxide Polymeric Micelles as Antitumoral Agents for 4T1 Breast Cancer
title_fullStr Development and Evaluation of 2-Amino-7-Fluorophenazine 5,10-Dioxide Polymeric Micelles as Antitumoral Agents for 4T1 Breast Cancer
title_full_unstemmed Development and Evaluation of 2-Amino-7-Fluorophenazine 5,10-Dioxide Polymeric Micelles as Antitumoral Agents for 4T1 Breast Cancer
title_sort Development and Evaluation of 2-Amino-7-Fluorophenazine 5,10-Dioxide Polymeric Micelles as Antitumoral Agents for 4T1 Breast Cancer
dc.creator.none.fl_str_mv Lecot, Nicole
Dávila Belzunce, María Belén
Sánchez, Carina
Fernández, Marcelo
González, Mercedes
Cabral, Pablo
Cerecetto, Hugo
Glisoni, Romina Julieta
author Lecot, Nicole
author_facet Lecot, Nicole
Dávila Belzunce, María Belén
Sánchez, Carina
Fernández, Marcelo
González, Mercedes
Cabral, Pablo
Cerecetto, Hugo
Glisoni, Romina Julieta
author_role author
author2 Dávila Belzunce, María Belén
Sánchez, Carina
Fernández, Marcelo
González, Mercedes
Cabral, Pablo
Cerecetto, Hugo
Glisoni, Romina Julieta
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv 10-DIOXIDE
4T1-TUMOR MODEL
AMPHIPHILIC PRISTINE POLYMERIC MICELLES
BIOREDUCTIVE-DRUG
IN VIVO ANTITUMORAL ACTIVITY
PHENAZINE-5
topic 10-DIOXIDE
4T1-TUMOR MODEL
AMPHIPHILIC PRISTINE POLYMERIC MICELLES
BIOREDUCTIVE-DRUG
IN VIVO ANTITUMORAL ACTIVITY
PHENAZINE-5
purl_subject.fl_str_mv https://purl.org/becyt/ford/2.10
https://purl.org/becyt/ford/2
dc.description.none.fl_txt_mv 2-Amino-7-fluorophenazine 5,10-dioxide (FNZ) is a bioreducible prodrug, poorly soluble in water, with potential anticancer activity on hypoxic-tumors. This poor solubility limits its potential applications in clinic. Amphiphilic pristine polymeric micelles (PMs) based on triblock copolymers Pluronic® and Tetronic®, glycosylated derivatives and their mixtures with preformed-liposomes (LPS), were analyzed as strategies to improve the bioavailability of FNZ. FNZ encapsulations were performed and the obtaining nanostructures were characterized using UV-visible spectroscopy (UV- VIS), Transmission Electron Microscopy (TEM), Fourier transform infrared analysis and Dynamic Light Scattering (DLS). The most promising nanoformulations were analyzed for their potential toxicity and pharmacologically, at 20 mg/kg FNZ-doses, in a stage-IV murine metastatic-breast tumor model. The results revealed that the solubility of the encapsulated-FNZ increased up to seven times and the analysis (UV-VIS, DLS and TEM) confirmed the interaction between vehicles and FNZ. In all the cases appropriate encapsulation efficiencies (up to 70%), monodisperse nanometric particle sizes (PDI = 0.180–0.335), adequate Z-potentials (-1.59 to -26.4 mV), stabilities and spherical morphologies were obtained. The in vitro profile of FNZ controlled releases corresponded mainly to a kinetic Higuchi model. The in vitro/in vivo biological studies revealed non-toxicity and relevant tumor-weight diminution (up to 61%).
Fil: Lecot, Nicole. Universidad de la República; Uruguay
Fil: Dávila Belzunce, María Belén. Universidad de la República; Uruguay
Fil: Sánchez, Carina. Universidad de la República; Uruguay
Fil: Fernández, Marcelo. Universidad de la República; Uruguay
Fil: González, Mercedes. Universidad de la República; Uruguay
Fil: Cabral, Pablo. Universidad de la República; Uruguay
Fil: Cerecetto, Hugo. Universidad de la República; Uruguay
Fil: Glisoni, Romina Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; Argentina
description 2-Amino-7-fluorophenazine 5,10-dioxide (FNZ) is a bioreducible prodrug, poorly soluble in water, with potential anticancer activity on hypoxic-tumors. This poor solubility limits its potential applications in clinic. Amphiphilic pristine polymeric micelles (PMs) based on triblock copolymers Pluronic® and Tetronic®, glycosylated derivatives and their mixtures with preformed-liposomes (LPS), were analyzed as strategies to improve the bioavailability of FNZ. FNZ encapsulations were performed and the obtaining nanostructures were characterized using UV-visible spectroscopy (UV- VIS), Transmission Electron Microscopy (TEM), Fourier transform infrared analysis and Dynamic Light Scattering (DLS). The most promising nanoformulations were analyzed for their potential toxicity and pharmacologically, at 20 mg/kg FNZ-doses, in a stage-IV murine metastatic-breast tumor model. The results revealed that the solubility of the encapsulated-FNZ increased up to seven times and the analysis (UV-VIS, DLS and TEM) confirmed the interaction between vehicles and FNZ. In all the cases appropriate encapsulation efficiencies (up to 70%), monodisperse nanometric particle sizes (PDI = 0.180–0.335), adequate Z-potentials (-1.59 to -26.4 mV), stabilities and spherical morphologies were obtained. The in vitro profile of FNZ controlled releases corresponded mainly to a kinetic Higuchi model. The in vitro/in vivo biological studies revealed non-toxicity and relevant tumor-weight diminution (up to 61%).
publishDate 2021
dc.date.none.fl_str_mv 2021-01
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/11336/170609
Lecot, Nicole; Dávila Belzunce, María Belén; Sánchez, Carina; Fernández, Marcelo; González, Mercedes; et al.; Development and Evaluation of 2-Amino-7-Fluorophenazine 5,10-Dioxide Polymeric Micelles as Antitumoral Agents for 4T1 Breast Cancer; MDPI; Polymers; 14; 1; 1-2021; 1-14
2073-4360
CONICET Digital
CONICET
url http://hdl.handle.net/11336/170609
identifier_str_mv Lecot, Nicole; Dávila Belzunce, María Belén; Sánchez, Carina; Fernández, Marcelo; González, Mercedes; et al.; Development and Evaluation of 2-Amino-7-Fluorophenazine 5,10-Dioxide Polymeric Micelles as Antitumoral Agents for 4T1 Breast Cancer; MDPI; Polymers; 14; 1; 1-2021; 1-14
2073-4360
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.mdpi.com/2073-4360/14/1/71
info:eu-repo/semantics/altIdentifier/doi/10.3390/polym14010071
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
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 12.993085

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