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dc.contributor.author
Taich, Paula Juliana
dc.contributor.author
Moretton, Marcela Analía
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del Sole, Maria Jose
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Winter, Ursula Andrea
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Bernabeu, Ezequiel Adrian
dc.contributor.author
Croxatto, Juan Oscar
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Oppezzo, Javier
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Williams, Gustavo
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Chantada, Guillermo Luis
dc.contributor.author
Chiappetta, Diego Andrés
dc.contributor.author
Schaiquevich, Paula Susana
dc.date.available
2018-05-31T14:51:44Z
dc.date.issued
2016-10
dc.identifier.citation
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
dc.identifier.issn
0927-7765
dc.identifier.uri
http://hdl.handle.net/11336/46793
dc.description.abstract
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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Elsevier Science
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Topotecan
dc.subject
Hydrogels
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Cytotoxicity
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Retinoblastoma
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Rabbits
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Farmacología y Farmacia
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Sustained-release hydrogels of topotecan for retinoblastoma
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-05-30T17:17:31Z
dc.journal.volume
146
dc.journal.pagination
624-631
dc.journal.pais
Países Bajos
dc.journal.ciudad
Amsterdam
dc.description.fil
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
dc.description.fil
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
dc.description.fil
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
dc.description.fil
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
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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
dc.description.fil
Fil: Croxatto, Juan Oscar. Fundación Oftalmología Argentina "J. Malbrán"; Argentina
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Fil: Oppezzo, Javier. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina
dc.description.fil
Fil: Williams, Gustavo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
dc.description.fil
Fil: Chantada, Guillermo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
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
dc.description.fil
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
dc.journal.title
Colloids and Surfaces B: Biointerfaces
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://dx.doi.org/10.1016/j.colsurfb.2016.07.001
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0927776516304933
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