Sustained-release hydrogels of topotecan for retinoblastoma

Autores
Taich, Paula Juliana; Moretton, Marcela Analía; del Sole, Maria Jose; Winter, Ursula Andrea; Bernabeu, Ezequiel Adrian; Croxatto, Juan Oscar; Oppezzo, Javier; Williams, Gustavo; Chantada, Guillermo Luis; Chiappetta, Diego Andrés; Schaiquevich, Paula Susana
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Treatment of retinoblastoma, the most common primary ocular malignancy in children, has greatly improved over the last decade. Still, new devices for chemotherapy are needed to achieve better tumor control. The aim of this project was to develop an ocular drug delivery system for topotecan (TPT) loaded in biocompatible hydrogels of poly(ε-caprolactone)-poly(ethyleneglycol)-poly(ε-caprolactone) block copolymers (PCL-PEG-PCL) for sustained TPT release in the vitreous humor. Hydrogels were prepared from TPT and synthesized PCL-PEG-PCL copolymers. Rheological properties and in vitro and in vivo TPT release were studied. Hydrogel cytotoxicity was evaluated in retinoblastoma cells as a surrogate for efficacy and TPT vitreous pharmacokinetics and systemic as well as ocular toxicity were evaluated in rabbits. The pseudoplastic behavior of the hydrogels makes them suitable for intraocular administration. In vitro release profiles showed a sustained release of TPT from PCL-PEG-PCL up to 7 days and drug loading did not affect the release pattern. Blank hydrogels did not affect retinoblastoma cell viability but 0.4% (w/w) TPT-loaded hydrogel was highly cytotoxic for at least 7 days. After intravitreal injection, TPT vitreous concentrations were sustained above the pharmacologically active concentration. One month after injection, animals with blank or TPT-loaded hydrogels showed no systemic toxicity or retinal impairment on fundus examination, electroretinographic, and histopathological assessments. These novel TPT-hydrogels can deliver sustained concentrations of active drug into the vitreous with excellent biocompatibility in vivo and pronounced cytotoxic activity in retinoblastoma cells and may become an additional strategy for intraocular retinoblastoma treatment.
Fil: Taich, Paula Juliana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Moretton, Marcela Analía. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina
Fil: del Sole, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Winter, Ursula Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Bernabeu, Ezequiel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina
Fil: Croxatto, Juan Oscar. Fundación Oftalmología Argentina "J. Malbrán"; Argentina
Fil: Oppezzo, Javier. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina
Fil: Williams, Gustavo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Chantada, Guillermo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Chiappetta, Diego Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina
Fil: Schaiquevich, Paula Susana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Materia
Topotecan
Hydrogels
Cytotoxicity
Retinoblastoma
Rabbits
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:11336/46793
Acceder
id CONICETDig_cf9dcc1f5a3f01024bc2740bf74b7f4c
oai_identifier_str oai:ri.conicet.gov.ar:11336/46793
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Sustained-release hydrogels of topotecan for retinoblastomaTaich, Paula JulianaMoretton, Marcela Analíadel Sole, Maria JoseWinter, Ursula AndreaBernabeu, Ezequiel AdrianCroxatto, Juan OscarOppezzo, JavierWilliams, GustavoChantada, Guillermo LuisChiappetta, Diego AndrésSchaiquevich, Paula SusanaTopotecanHydrogelsCytotoxicityRetinoblastomaRabbitshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Treatment of retinoblastoma, the most common primary ocular malignancy in children, has greatly improved over the last decade. Still, new devices for chemotherapy are needed to achieve better tumor control. The aim of this project was to develop an ocular drug delivery system for topotecan (TPT) loaded in biocompatible hydrogels of poly(ε-caprolactone)-poly(ethyleneglycol)-poly(ε-caprolactone) block copolymers (PCL-PEG-PCL) for sustained TPT release in the vitreous humor. Hydrogels were prepared from TPT and synthesized PCL-PEG-PCL copolymers. Rheological properties and in vitro and in vivo TPT release were studied. Hydrogel cytotoxicity was evaluated in retinoblastoma cells as a surrogate for efficacy and TPT vitreous pharmacokinetics and systemic as well as ocular toxicity were evaluated in rabbits. The pseudoplastic behavior of the hydrogels makes them suitable for intraocular administration. In vitro release profiles showed a sustained release of TPT from PCL-PEG-PCL up to 7 days and drug loading did not affect the release pattern. Blank hydrogels did not affect retinoblastoma cell viability but 0.4% (w/w) TPT-loaded hydrogel was highly cytotoxic for at least 7 days. After intravitreal injection, TPT vitreous concentrations were sustained above the pharmacologically active concentration. One month after injection, animals with blank or TPT-loaded hydrogels showed no systemic toxicity or retinal impairment on fundus examination, electroretinographic, and histopathological assessments. These novel TPT-hydrogels can deliver sustained concentrations of active drug into the vitreous with excellent biocompatibility in vivo and pronounced cytotoxic activity in retinoblastoma cells and may become an additional strategy for intraocular retinoblastoma treatment.Fil: Taich, Paula Juliana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Moretton, Marcela Analía. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; ArgentinaFil: del Sole, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Winter, Ursula Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Bernabeu, Ezequiel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; ArgentinaFil: Croxatto, Juan Oscar. Fundación Oftalmología Argentina "J. Malbrán"; ArgentinaFil: Oppezzo, Javier. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; ArgentinaFil: Williams, Gustavo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Chantada, Guillermo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Chiappetta, Diego Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; ArgentinaFil: Schaiquevich, Paula Susana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaElsevier Science2016-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/46793Taich, Paula Juliana; Moretton, Marcela Analía; del Sole, Maria Jose; Winter, Ursula Andrea; Bernabeu, Ezequiel Adrian; et al.; Sustained-release hydrogels of topotecan for retinoblastoma; Elsevier Science; Colloids and Surfaces B: Biointerfaces; 146; 10-2016; 624-6310927-7765CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.colsurfb.2016.07.001info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0927776516304933info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:01:03Zoai:ri.conicet.gov.ar:11336/46793instacron: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 10:01:04.176CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Sustained-release hydrogels of topotecan for retinoblastoma
title Sustained-release hydrogels of topotecan for retinoblastoma
spellingShingle Sustained-release hydrogels of topotecan for retinoblastoma
Taich, Paula Juliana
Topotecan
Hydrogels
Cytotoxicity
Retinoblastoma
Rabbits
title_short Sustained-release hydrogels of topotecan for retinoblastoma
title_full Sustained-release hydrogels of topotecan for retinoblastoma
title_fullStr Sustained-release hydrogels of topotecan for retinoblastoma
title_full_unstemmed Sustained-release hydrogels of topotecan for retinoblastoma
title_sort Sustained-release hydrogels of topotecan for retinoblastoma
dc.creator.none.fl_str_mv Taich, Paula Juliana
Moretton, Marcela Analía
del Sole, Maria Jose
Winter, Ursula Andrea
Bernabeu, Ezequiel Adrian
Croxatto, Juan Oscar
Oppezzo, Javier
Williams, Gustavo
Chantada, Guillermo Luis
Chiappetta, Diego Andrés
Schaiquevich, Paula Susana
author Taich, Paula Juliana
author_facet Taich, Paula Juliana
Moretton, Marcela Analía
del Sole, Maria Jose
Winter, Ursula Andrea
Bernabeu, Ezequiel Adrian
Croxatto, Juan Oscar
Oppezzo, Javier
Williams, Gustavo
Chantada, Guillermo Luis
Chiappetta, Diego Andrés
Schaiquevich, Paula Susana
author_role author
author2 Moretton, Marcela Analía
del Sole, Maria Jose
Winter, Ursula Andrea
Bernabeu, Ezequiel Adrian
Croxatto, Juan Oscar
Oppezzo, Javier
Williams, Gustavo
Chantada, Guillermo Luis
Chiappetta, Diego Andrés
Schaiquevich, Paula Susana
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Topotecan
Hydrogels
Cytotoxicity
Retinoblastoma
Rabbits
topic Topotecan
Hydrogels
Cytotoxicity
Retinoblastoma
Rabbits
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Treatment of retinoblastoma, the most common primary ocular malignancy in children, has greatly improved over the last decade. Still, new devices for chemotherapy are needed to achieve better tumor control. The aim of this project was to develop an ocular drug delivery system for topotecan (TPT) loaded in biocompatible hydrogels of poly(ε-caprolactone)-poly(ethyleneglycol)-poly(ε-caprolactone) block copolymers (PCL-PEG-PCL) for sustained TPT release in the vitreous humor. Hydrogels were prepared from TPT and synthesized PCL-PEG-PCL copolymers. Rheological properties and in vitro and in vivo TPT release were studied. Hydrogel cytotoxicity was evaluated in retinoblastoma cells as a surrogate for efficacy and TPT vitreous pharmacokinetics and systemic as well as ocular toxicity were evaluated in rabbits. The pseudoplastic behavior of the hydrogels makes them suitable for intraocular administration. In vitro release profiles showed a sustained release of TPT from PCL-PEG-PCL up to 7 days and drug loading did not affect the release pattern. Blank hydrogels did not affect retinoblastoma cell viability but 0.4% (w/w) TPT-loaded hydrogel was highly cytotoxic for at least 7 days. After intravitreal injection, TPT vitreous concentrations were sustained above the pharmacologically active concentration. One month after injection, animals with blank or TPT-loaded hydrogels showed no systemic toxicity or retinal impairment on fundus examination, electroretinographic, and histopathological assessments. These novel TPT-hydrogels can deliver sustained concentrations of active drug into the vitreous with excellent biocompatibility in vivo and pronounced cytotoxic activity in retinoblastoma cells and may become an additional strategy for intraocular retinoblastoma treatment.
Fil: Taich, Paula Juliana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Moretton, Marcela Analía. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina
Fil: del Sole, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Winter, Ursula Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Bernabeu, Ezequiel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina
Fil: Croxatto, Juan Oscar. Fundación Oftalmología Argentina "J. Malbrán"; Argentina
Fil: Oppezzo, Javier. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina
Fil: Williams, Gustavo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Chantada, Guillermo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Chiappetta, Diego Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina
Fil: Schaiquevich, Paula Susana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
description Treatment of retinoblastoma, the most common primary ocular malignancy in children, has greatly improved over the last decade. Still, new devices for chemotherapy are needed to achieve better tumor control. The aim of this project was to develop an ocular drug delivery system for topotecan (TPT) loaded in biocompatible hydrogels of poly(ε-caprolactone)-poly(ethyleneglycol)-poly(ε-caprolactone) block copolymers (PCL-PEG-PCL) for sustained TPT release in the vitreous humor. Hydrogels were prepared from TPT and synthesized PCL-PEG-PCL copolymers. Rheological properties and in vitro and in vivo TPT release were studied. Hydrogel cytotoxicity was evaluated in retinoblastoma cells as a surrogate for efficacy and TPT vitreous pharmacokinetics and systemic as well as ocular toxicity were evaluated in rabbits. The pseudoplastic behavior of the hydrogels makes them suitable for intraocular administration. In vitro release profiles showed a sustained release of TPT from PCL-PEG-PCL up to 7 days and drug loading did not affect the release pattern. Blank hydrogels did not affect retinoblastoma cell viability but 0.4% (w/w) TPT-loaded hydrogel was highly cytotoxic for at least 7 days. After intravitreal injection, TPT vitreous concentrations were sustained above the pharmacologically active concentration. One month after injection, animals with blank or TPT-loaded hydrogels showed no systemic toxicity or retinal impairment on fundus examination, electroretinographic, and histopathological assessments. These novel TPT-hydrogels can deliver sustained concentrations of active drug into the vitreous with excellent biocompatibility in vivo and pronounced cytotoxic activity in retinoblastoma cells and may become an additional strategy for intraocular retinoblastoma treatment.
publishDate 2016
dc.date.none.fl_str_mv 2016-10
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/11336/46793
Taich, Paula Juliana; Moretton, Marcela Analía; del Sole, Maria Jose; Winter, Ursula Andrea; Bernabeu, Ezequiel Adrian; et al.; Sustained-release hydrogels of topotecan for retinoblastoma; Elsevier Science; Colloids and Surfaces B: Biointerfaces; 146; 10-2016; 624-631
0927-7765
CONICET Digital
CONICET
url http://hdl.handle.net/11336/46793
identifier_str_mv Taich, Paula Juliana; Moretton, Marcela Analía; del Sole, Maria Jose; Winter, Ursula Andrea; Bernabeu, Ezequiel Adrian; et al.; Sustained-release hydrogels of topotecan for retinoblastoma; Elsevier Science; Colloids and Surfaces B: Biointerfaces; 146; 10-2016; 624-631
0927-7765
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.colsurfb.2016.07.001
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0927776516304933
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
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
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