Increased delivery of chemotherapy to the vitreous by inhibition of the blood-retinal barrier
- Autores
- Pascual-Pasto, Guillem; Olaciregui, Nagore G.; Opezzo, Javier A. W.; Castillo Ecija, Helena; Cuadrado Vilanova, Maria; Paco, Sonia; Rivero, Ezequiel Mariano; Vila Ubach, Monica; Restrepo Perdomo, Camilo A.; Torrebadell, Montserrat; Suñol, Mariona; Schaiquevich, Paula Susana; Mora, Jaume; Bramuglia, Guillermo Federico; Chantada, Guillermo Luis; Carcaboso, Angel M.
- Año de publicación
- 2017
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Treatment of retinoblastoma -a pediatric cancer of the developing retina- might benefit from strategies to inhibit the blood-retinal barrier (BRB). The potent anticancer agent topotecan is a substrate of efflux transporters BCRP and P-gp, which are expressed at the BRB to restrict vitreous and retinal distribution of xenobiotics. In this work we have studied vitreous and retinal distribution, tumor accumulation and antitumor activity of topotecan, using pantoprazole as inhibitor of BCRP and P-gp. We used rabbit and mouse eyes as BRB models and patient-derived xenografts as retinoblastoma models. To validate the rabbit BRB model we stained BCRP and P-gp in the retinal vessels. Using intravitreous microdialysis we showed that the penetration of the rabbit vitreous by lactone topotecan increased significantly upon concomitant administration of pantoprazole (P = 0.0285). Pantoprazole also increased topotecan penetration of the mouse vitreous, measured as the vitreous-to-plasma topotecan concentration ratio at the steady state (P = 0.0246). Pantoprazole increased topotecan antitumor efficacy and intracellular penetration in retinoblastoma in vitro, but did not enhance intratumor drug distribution and survival in mice bearing the intraocular human tumor HSJD-RBT-2. Anatomical differences with the clinical setting likely limited our in vivo study, since xenografts were poorly vascularized masses that loaded most of the vitreous compartment. We conclude that pharmacological modulation of the BRB is feasible, enhances anticancer drug distribution into the vitreous and might have clinical implications in retinoblastoma.
Fil: Pascual-Pasto, Guillem. Hospital Sant Joan de Deu Barcelona; España. Institut de Recerca Sant Joan de Deu; España
Fil: Olaciregui, Nagore G.. Hospital Sant Joan de Deu Barcelona; España. Institut de Recerca Sant Joan de Deu; España
Fil: Opezzo, Javier A. W.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina
Fil: Castillo Ecija, Helena. Hospital Sant Joan de Deu Barcelona; España. Institut de Recerca Sant Joan de Deu; España
Fil: Cuadrado Vilanova, Maria. Hospital Sant Joan de Deu Barcelona; España. Institut de Recerca Sant Joan de Deu; España
Fil: Paco, Sonia. Hospital Sant Joan de Deu Barcelona; España. Institut de Recerca Sant Joan de Deu; España
Fil: Rivero, Ezequiel Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Vila Ubach, Monica. Hospital Sant Joan de Deu Barcelona; España. Institut de Recerca Sant Joan de Deu; España
Fil: Restrepo Perdomo, Camilo A.. Hospital Sant Joan de Deu Barcelona; España
Fil: Torrebadell, Montserrat. Hospital Sant Joan de Deu Barcelona; España. Institut de Recerca Sant Joan de Deu; España
Fil: Suñol, Mariona. Hospital Sant Joan de Deu Barcelona; España
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
Fil: Mora, Jaume. Hospital Sant Joan de Deu Barcelona; España. Institut de Recerca Sant Joan de Deu; España
Fil: Bramuglia, Guillermo Federico. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina
Fil: Chantada, Guillermo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Hospital Sant Joan de Deu Barcelona; España. Institut de Recerca Sant Joan de Deu; España
Fil: Carcaboso, Angel M.. Hospital Sant Joan de Deu Barcelona; España. Institut de Recerca Sant Joan de Deu; España - Materia
-
ABC TRANSPORTERS
ABCB1/P-GP
ABCG2/BCRP
BCRP
BLOOD-RETINAL BARRIER
DELIVERY
DISTRIBUTION
MICRODIALYSIS
P-GP
PANTOPRAZOLE
PEDIATRIC CANCER
RABBIT
RETINA
RETINOBLASTOMA
TOPOTECAN
VITREOUS
XENOGRAFT - 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:11336/85225
Ver los metadatos del registro completo
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oai:ri.conicet.gov.ar:11336/85225 |
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spelling |
Increased delivery of chemotherapy to the vitreous by inhibition of the blood-retinal barrierPascual-Pasto, GuillemOlaciregui, Nagore G.Opezzo, Javier A. W.Castillo Ecija, HelenaCuadrado Vilanova, MariaPaco, SoniaRivero, Ezequiel MarianoVila Ubach, MonicaRestrepo Perdomo, Camilo A.Torrebadell, MontserratSuñol, MarionaSchaiquevich, Paula SusanaMora, JaumeBramuglia, Guillermo FedericoChantada, Guillermo LuisCarcaboso, Angel M.ABC TRANSPORTERSABCB1/P-GPABCG2/BCRPBCRPBLOOD-RETINAL BARRIERDELIVERYDISTRIBUTIONMICRODIALYSISP-GPPANTOPRAZOLEPEDIATRIC CANCERRABBITRETINARETINOBLASTOMATOPOTECANVITREOUSXENOGRAFThttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Treatment of retinoblastoma -a pediatric cancer of the developing retina- might benefit from strategies to inhibit the blood-retinal barrier (BRB). The potent anticancer agent topotecan is a substrate of efflux transporters BCRP and P-gp, which are expressed at the BRB to restrict vitreous and retinal distribution of xenobiotics. In this work we have studied vitreous and retinal distribution, tumor accumulation and antitumor activity of topotecan, using pantoprazole as inhibitor of BCRP and P-gp. We used rabbit and mouse eyes as BRB models and patient-derived xenografts as retinoblastoma models. To validate the rabbit BRB model we stained BCRP and P-gp in the retinal vessels. Using intravitreous microdialysis we showed that the penetration of the rabbit vitreous by lactone topotecan increased significantly upon concomitant administration of pantoprazole (P = 0.0285). Pantoprazole also increased topotecan penetration of the mouse vitreous, measured as the vitreous-to-plasma topotecan concentration ratio at the steady state (P = 0.0246). Pantoprazole increased topotecan antitumor efficacy and intracellular penetration in retinoblastoma in vitro, but did not enhance intratumor drug distribution and survival in mice bearing the intraocular human tumor HSJD-RBT-2. Anatomical differences with the clinical setting likely limited our in vivo study, since xenografts were poorly vascularized masses that loaded most of the vitreous compartment. We conclude that pharmacological modulation of the BRB is feasible, enhances anticancer drug distribution into the vitreous and might have clinical implications in retinoblastoma.Fil: Pascual-Pasto, Guillem. Hospital Sant Joan de Deu Barcelona; España. Institut de Recerca Sant Joan de Deu; EspañaFil: Olaciregui, Nagore G.. Hospital Sant Joan de Deu Barcelona; España. Institut de Recerca Sant Joan de Deu; EspañaFil: Opezzo, Javier A. W.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; ArgentinaFil: Castillo Ecija, Helena. Hospital Sant Joan de Deu Barcelona; España. Institut de Recerca Sant Joan de Deu; EspañaFil: Cuadrado Vilanova, Maria. Hospital Sant Joan de Deu Barcelona; España. Institut de Recerca Sant Joan de Deu; EspañaFil: Paco, Sonia. Hospital Sant Joan de Deu Barcelona; España. Institut de Recerca Sant Joan de Deu; EspañaFil: Rivero, Ezequiel Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Vila Ubach, Monica. Hospital Sant Joan de Deu Barcelona; España. Institut de Recerca Sant Joan de Deu; EspañaFil: Restrepo Perdomo, Camilo A.. Hospital Sant Joan de Deu Barcelona; EspañaFil: Torrebadell, Montserrat. Hospital Sant Joan de Deu Barcelona; España. Institut de Recerca Sant Joan de Deu; EspañaFil: Suñol, Mariona. Hospital Sant Joan de Deu Barcelona; EspañaFil: Schaiquevich, Paula Susana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Mora, Jaume. Hospital Sant Joan de Deu Barcelona; España. Institut de Recerca Sant Joan de Deu; EspañaFil: Bramuglia, Guillermo Federico. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; ArgentinaFil: Chantada, Guillermo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Hospital Sant Joan de Deu Barcelona; España. Institut de Recerca Sant Joan de Deu; EspañaFil: Carcaboso, Angel M.. Hospital Sant Joan de Deu Barcelona; España. Institut de Recerca Sant Joan de Deu; EspañaElsevier Science2017-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/85225Pascual-Pasto, Guillem; Olaciregui, Nagore G.; Opezzo, Javier A. W.; Castillo Ecija, Helena; Cuadrado Vilanova, Maria; et al.; Increased delivery of chemotherapy to the vitreous by inhibition of the blood-retinal barrier; Elsevier Science; Journal of Controlled Release; 264; 10-2017; 34-440168-3659CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.jconrel.2017.08.018info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S016836591730785Xinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:34:47Zoai:ri.conicet.gov.ar:11336/85225instacron: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 09:34:48.053CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Increased delivery of chemotherapy to the vitreous by inhibition of the blood-retinal barrier |
title |
Increased delivery of chemotherapy to the vitreous by inhibition of the blood-retinal barrier |
spellingShingle |
Increased delivery of chemotherapy to the vitreous by inhibition of the blood-retinal barrier Pascual-Pasto, Guillem ABC TRANSPORTERS ABCB1/P-GP ABCG2/BCRP BCRP BLOOD-RETINAL BARRIER DELIVERY DISTRIBUTION MICRODIALYSIS P-GP PANTOPRAZOLE PEDIATRIC CANCER RABBIT RETINA RETINOBLASTOMA TOPOTECAN VITREOUS XENOGRAFT |
title_short |
Increased delivery of chemotherapy to the vitreous by inhibition of the blood-retinal barrier |
title_full |
Increased delivery of chemotherapy to the vitreous by inhibition of the blood-retinal barrier |
title_fullStr |
Increased delivery of chemotherapy to the vitreous by inhibition of the blood-retinal barrier |
title_full_unstemmed |
Increased delivery of chemotherapy to the vitreous by inhibition of the blood-retinal barrier |
title_sort |
Increased delivery of chemotherapy to the vitreous by inhibition of the blood-retinal barrier |
dc.creator.none.fl_str_mv |
Pascual-Pasto, Guillem Olaciregui, Nagore G. Opezzo, Javier A. W. Castillo Ecija, Helena Cuadrado Vilanova, Maria Paco, Sonia Rivero, Ezequiel Mariano Vila Ubach, Monica Restrepo Perdomo, Camilo A. Torrebadell, Montserrat Suñol, Mariona Schaiquevich, Paula Susana Mora, Jaume Bramuglia, Guillermo Federico Chantada, Guillermo Luis Carcaboso, Angel M. |
author |
Pascual-Pasto, Guillem |
author_facet |
Pascual-Pasto, Guillem Olaciregui, Nagore G. Opezzo, Javier A. W. Castillo Ecija, Helena Cuadrado Vilanova, Maria Paco, Sonia Rivero, Ezequiel Mariano Vila Ubach, Monica Restrepo Perdomo, Camilo A. Torrebadell, Montserrat Suñol, Mariona Schaiquevich, Paula Susana Mora, Jaume Bramuglia, Guillermo Federico Chantada, Guillermo Luis Carcaboso, Angel M. |
author_role |
author |
author2 |
Olaciregui, Nagore G. Opezzo, Javier A. W. Castillo Ecija, Helena Cuadrado Vilanova, Maria Paco, Sonia Rivero, Ezequiel Mariano Vila Ubach, Monica Restrepo Perdomo, Camilo A. Torrebadell, Montserrat Suñol, Mariona Schaiquevich, Paula Susana Mora, Jaume Bramuglia, Guillermo Federico Chantada, Guillermo Luis Carcaboso, Angel M. |
author2_role |
author author author author author author author author author author author author author author author |
dc.subject.none.fl_str_mv |
ABC TRANSPORTERS ABCB1/P-GP ABCG2/BCRP BCRP BLOOD-RETINAL BARRIER DELIVERY DISTRIBUTION MICRODIALYSIS P-GP PANTOPRAZOLE PEDIATRIC CANCER RABBIT RETINA RETINOBLASTOMA TOPOTECAN VITREOUS XENOGRAFT |
topic |
ABC TRANSPORTERS ABCB1/P-GP ABCG2/BCRP BCRP BLOOD-RETINAL BARRIER DELIVERY DISTRIBUTION MICRODIALYSIS P-GP PANTOPRAZOLE PEDIATRIC CANCER RABBIT RETINA RETINOBLASTOMA TOPOTECAN VITREOUS XENOGRAFT |
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 -a pediatric cancer of the developing retina- might benefit from strategies to inhibit the blood-retinal barrier (BRB). The potent anticancer agent topotecan is a substrate of efflux transporters BCRP and P-gp, which are expressed at the BRB to restrict vitreous and retinal distribution of xenobiotics. In this work we have studied vitreous and retinal distribution, tumor accumulation and antitumor activity of topotecan, using pantoprazole as inhibitor of BCRP and P-gp. We used rabbit and mouse eyes as BRB models and patient-derived xenografts as retinoblastoma models. To validate the rabbit BRB model we stained BCRP and P-gp in the retinal vessels. Using intravitreous microdialysis we showed that the penetration of the rabbit vitreous by lactone topotecan increased significantly upon concomitant administration of pantoprazole (P = 0.0285). Pantoprazole also increased topotecan penetration of the mouse vitreous, measured as the vitreous-to-plasma topotecan concentration ratio at the steady state (P = 0.0246). Pantoprazole increased topotecan antitumor efficacy and intracellular penetration in retinoblastoma in vitro, but did not enhance intratumor drug distribution and survival in mice bearing the intraocular human tumor HSJD-RBT-2. Anatomical differences with the clinical setting likely limited our in vivo study, since xenografts were poorly vascularized masses that loaded most of the vitreous compartment. We conclude that pharmacological modulation of the BRB is feasible, enhances anticancer drug distribution into the vitreous and might have clinical implications in retinoblastoma. Fil: Pascual-Pasto, Guillem. Hospital Sant Joan de Deu Barcelona; España. Institut de Recerca Sant Joan de Deu; España Fil: Olaciregui, Nagore G.. Hospital Sant Joan de Deu Barcelona; España. Institut de Recerca Sant Joan de Deu; España Fil: Opezzo, Javier A. W.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina Fil: Castillo Ecija, Helena. Hospital Sant Joan de Deu Barcelona; España. Institut de Recerca Sant Joan de Deu; España Fil: Cuadrado Vilanova, Maria. Hospital Sant Joan de Deu Barcelona; España. Institut de Recerca Sant Joan de Deu; España Fil: Paco, Sonia. Hospital Sant Joan de Deu Barcelona; España. Institut de Recerca Sant Joan de Deu; España Fil: Rivero, Ezequiel Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Vila Ubach, Monica. Hospital Sant Joan de Deu Barcelona; España. Institut de Recerca Sant Joan de Deu; España Fil: Restrepo Perdomo, Camilo A.. Hospital Sant Joan de Deu Barcelona; España Fil: Torrebadell, Montserrat. Hospital Sant Joan de Deu Barcelona; España. Institut de Recerca Sant Joan de Deu; España Fil: Suñol, Mariona. Hospital Sant Joan de Deu Barcelona; España 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 Fil: Mora, Jaume. Hospital Sant Joan de Deu Barcelona; España. Institut de Recerca Sant Joan de Deu; España Fil: Bramuglia, Guillermo Federico. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina Fil: Chantada, Guillermo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Hospital Sant Joan de Deu Barcelona; España. Institut de Recerca Sant Joan de Deu; España Fil: Carcaboso, Angel M.. Hospital Sant Joan de Deu Barcelona; España. Institut de Recerca Sant Joan de Deu; España |
description |
Treatment of retinoblastoma -a pediatric cancer of the developing retina- might benefit from strategies to inhibit the blood-retinal barrier (BRB). The potent anticancer agent topotecan is a substrate of efflux transporters BCRP and P-gp, which are expressed at the BRB to restrict vitreous and retinal distribution of xenobiotics. In this work we have studied vitreous and retinal distribution, tumor accumulation and antitumor activity of topotecan, using pantoprazole as inhibitor of BCRP and P-gp. We used rabbit and mouse eyes as BRB models and patient-derived xenografts as retinoblastoma models. To validate the rabbit BRB model we stained BCRP and P-gp in the retinal vessels. Using intravitreous microdialysis we showed that the penetration of the rabbit vitreous by lactone topotecan increased significantly upon concomitant administration of pantoprazole (P = 0.0285). Pantoprazole also increased topotecan penetration of the mouse vitreous, measured as the vitreous-to-plasma topotecan concentration ratio at the steady state (P = 0.0246). Pantoprazole increased topotecan antitumor efficacy and intracellular penetration in retinoblastoma in vitro, but did not enhance intratumor drug distribution and survival in mice bearing the intraocular human tumor HSJD-RBT-2. Anatomical differences with the clinical setting likely limited our in vivo study, since xenografts were poorly vascularized masses that loaded most of the vitreous compartment. We conclude that pharmacological modulation of the BRB is feasible, enhances anticancer drug distribution into the vitreous and might have clinical implications in retinoblastoma. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-10 |
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/11336/85225 Pascual-Pasto, Guillem; Olaciregui, Nagore G.; Opezzo, Javier A. W.; Castillo Ecija, Helena; Cuadrado Vilanova, Maria; et al.; Increased delivery of chemotherapy to the vitreous by inhibition of the blood-retinal barrier; Elsevier Science; Journal of Controlled Release; 264; 10-2017; 34-44 0168-3659 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/85225 |
identifier_str_mv |
Pascual-Pasto, Guillem; Olaciregui, Nagore G.; Opezzo, Javier A. W.; Castillo Ecija, Helena; Cuadrado Vilanova, Maria; et al.; Increased delivery of chemotherapy to the vitreous by inhibition of the blood-retinal barrier; Elsevier Science; Journal of Controlled Release; 264; 10-2017; 34-44 0168-3659 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.jconrel.2017.08.018 info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S016836591730785X |
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 |
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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1844613078786768896 |
score |
13.070432 |