Combined Microdialysis-Tumor Homogenate Method for the Study of the Steady State Compartmental Distribution of a Hydrophobic Anticancer Drug in Patient-Derived Xenografts

Autores
Monterrubio, Carles; Paco, Sonia; Vila Ubach, Mónica; Rodríguez, Eva; Glisoni, Romina Julieta; Lavarino, Cinzia; Schaiquevich, Paula Susana; Sosnik, Alejandro; Mora, Jaume; Carcaboso, Ángel M.
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
PURPOSE: To develop a reproducible microdialysis-tumor homogenate method for the study of the intratumor distribution of a highly hydrophobic anticancer drug (SN-38; 7-ethyl-10-hydroxycamptothecin) in neuroblastoma patient-derived xenografts. METHODS: We studied the nonspecific binding of SN-38 to the microdialysis tubing in the presence of 2-hydroxypropyl-beta-cyclodextrin (HPBCD) in the perfusate. We calibrated the microdialysis probes by the zero flow rate (ZFR) method and calculated the enhancement factor (f = extrapolated SN-38 concentration at the ZFR / SN-38 concentration in the dialysed solution) of HPBCD. We characterized the extravasation of HPBCD to tumors engrafted in mice. In vivo microdialysis and terminal homogenate data at the steady state (subcutaneous pump infusions) were used to calculate the volume of distribution of unbound SN-38 (Vu,tumor) in neuroblastoma. RESULTS: HPBCD (10% w/v) in the perfusate prevented the nonspecific binding of SN-38 to the microdialysis probe and enhanced SN-38 recovery (f = 1.86). The extravasation of HPBCD in the tumor during microdialysis was lower than 1%. Vu,tumor values were above 3 mL/g tumor for both neuroblastoma models and suggested efficient cellular penetration of SN-38. CONCLUSIONS: The method contributes to overcome the limitations of the microdialysis technique in hydrophobic drugs and provides a powerful tool to characterize compartmental anticancer drug distribution in xenografts.
Fil: Monterrubio, Carles. Hospital Sant Joan de Déu Barcelona; España. Fundació Sant Joan de Déu; España
Fil: Paco, Sonia. Hospital Sant Joan de Déu Barcelona; España. Fundació Sant Joan de Déu; España
Fil: Vila Ubach, Mónica. Hospital Sant Joan de Déu Barcelona; España. Fundació Sant Joan de Déu; España
Fil: Rodríguez, Eva. Hospital Sant Joan de Déu Barcelona; España. Fundació Sant Joan de Déu; España
Fil: Glisoni, Romina Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina
Fil: Lavarino, Cinzia. Technion - Israel Institute of Technology; Israel
Fil: Schaiquevich, Paula Susana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina
Fil: Sosnik, Alejandro. Hospital Sant Joan de Déu Barcelona; España. Fundació Sant Joan de Déu; España
Fil: Mora, Jaume. Hospital Sant Joan de Déu Barcelona; España. Fundació Sant Joan de Déu; España
Fil: Carcaboso, Ángel M.. Hospital Sant Joan de Déu Barcelona; España. Fundació Sant Joan de Déu; España
Materia
Microdialysis
Oncology
Drug Distribution
Drug Penetration
Hydrophobic Anticancer Drugs
Microdialysis
Neuroblastoma
Patient-Derived Xenograft (Pdx)
Sn-38
Solid Tumor
Steady State
Tumor Homogenate
Tumor Microenvironment
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:11336/33112
Acceder
id CONICETDig_def8162efe3e68b300b05f5f0a6cd711
oai_identifier_str oai:ri.conicet.gov.ar:11336/33112
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Combined Microdialysis-Tumor Homogenate Method for the Study of the Steady State Compartmental Distribution of a Hydrophobic Anticancer Drug in Patient-Derived XenograftsMonterrubio, CarlesPaco, SoniaVila Ubach, MónicaRodríguez, EvaGlisoni, Romina JulietaLavarino, CinziaSchaiquevich, Paula SusanaSosnik, AlejandroMora, JaumeCarcaboso, Ángel M.MicrodialysisOncologyDrug DistributionDrug PenetrationHydrophobic Anticancer DrugsMicrodialysisNeuroblastomaPatient-Derived Xenograft (Pdx)Sn-38Solid TumorSteady StateTumor HomogenateTumor Microenvironmenthttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3PURPOSE: To develop a reproducible microdialysis-tumor homogenate method for the study of the intratumor distribution of a highly hydrophobic anticancer drug (SN-38; 7-ethyl-10-hydroxycamptothecin) in neuroblastoma patient-derived xenografts. METHODS: We studied the nonspecific binding of SN-38 to the microdialysis tubing in the presence of 2-hydroxypropyl-beta-cyclodextrin (HPBCD) in the perfusate. We calibrated the microdialysis probes by the zero flow rate (ZFR) method and calculated the enhancement factor (f = extrapolated SN-38 concentration at the ZFR / SN-38 concentration in the dialysed solution) of HPBCD. We characterized the extravasation of HPBCD to tumors engrafted in mice. In vivo microdialysis and terminal homogenate data at the steady state (subcutaneous pump infusions) were used to calculate the volume of distribution of unbound SN-38 (Vu,tumor) in neuroblastoma. RESULTS: HPBCD (10% w/v) in the perfusate prevented the nonspecific binding of SN-38 to the microdialysis probe and enhanced SN-38 recovery (f = 1.86). The extravasation of HPBCD in the tumor during microdialysis was lower than 1%. Vu,tumor values were above 3 mL/g tumor for both neuroblastoma models and suggested efficient cellular penetration of SN-38. CONCLUSIONS: The method contributes to overcome the limitations of the microdialysis technique in hydrophobic drugs and provides a powerful tool to characterize compartmental anticancer drug distribution in xenografts.Fil: Monterrubio, Carles. Hospital Sant Joan de Déu Barcelona; España. Fundació Sant Joan de Déu; EspañaFil: Paco, Sonia. Hospital Sant Joan de Déu Barcelona; España. Fundació Sant Joan de Déu; EspañaFil: Vila Ubach, Mónica. Hospital Sant Joan de Déu Barcelona; España. Fundació Sant Joan de Déu; EspañaFil: Rodríguez, Eva. Hospital Sant Joan de Déu Barcelona; España. Fundació Sant Joan de Déu; EspañaFil: Glisoni, Romina Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; ArgentinaFil: Lavarino, Cinzia. Technion - Israel Institute of Technology; IsraelFil: Schaiquevich, Paula Susana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; ArgentinaFil: Sosnik, Alejandro. Hospital Sant Joan de Déu Barcelona; España. Fundació Sant Joan de Déu; EspañaFil: Mora, Jaume. Hospital Sant Joan de Déu Barcelona; España. Fundació Sant Joan de Déu; EspañaFil: Carcaboso, Ángel M.. Hospital Sant Joan de Déu Barcelona; España. Fundació Sant Joan de Déu; EspañaSpringer2014-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/33112Schaiquevich, Paula Susana; Sosnik, Alejandro; Monterrubio, Carles; Carcaboso, Ángel M.; Lavarino, Cinzia; Rodríguez, Eva; et al.; Combined Microdialysis-Tumor Homogenate Method for the Study of the Steady State Compartmental Distribution of a Hydrophobic Anticancer Drug in Patient-Derived Xenografts; Springer; Pharmaceutical Research; 32; 9; 3-2014; 2889-29000724-87411573-904XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1007/s11095-015-1671-9info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007/s11095-015-1671-9info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:58:05Zoai:ri.conicet.gov.ar:11336/33112instacron: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 09:58:06.279CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Combined Microdialysis-Tumor Homogenate Method for the Study of the Steady State Compartmental Distribution of a Hydrophobic Anticancer Drug in Patient-Derived Xenografts
title Combined Microdialysis-Tumor Homogenate Method for the Study of the Steady State Compartmental Distribution of a Hydrophobic Anticancer Drug in Patient-Derived Xenografts
spellingShingle Combined Microdialysis-Tumor Homogenate Method for the Study of the Steady State Compartmental Distribution of a Hydrophobic Anticancer Drug in Patient-Derived Xenografts
Monterrubio, Carles
Microdialysis
Oncology
Drug Distribution
Drug Penetration
Hydrophobic Anticancer Drugs
Microdialysis
Neuroblastoma
Patient-Derived Xenograft (Pdx)
Sn-38
Solid Tumor
Steady State
Tumor Homogenate
Tumor Microenvironment
title_short Combined Microdialysis-Tumor Homogenate Method for the Study of the Steady State Compartmental Distribution of a Hydrophobic Anticancer Drug in Patient-Derived Xenografts
title_full Combined Microdialysis-Tumor Homogenate Method for the Study of the Steady State Compartmental Distribution of a Hydrophobic Anticancer Drug in Patient-Derived Xenografts
title_fullStr Combined Microdialysis-Tumor Homogenate Method for the Study of the Steady State Compartmental Distribution of a Hydrophobic Anticancer Drug in Patient-Derived Xenografts
title_full_unstemmed Combined Microdialysis-Tumor Homogenate Method for the Study of the Steady State Compartmental Distribution of a Hydrophobic Anticancer Drug in Patient-Derived Xenografts
title_sort Combined Microdialysis-Tumor Homogenate Method for the Study of the Steady State Compartmental Distribution of a Hydrophobic Anticancer Drug in Patient-Derived Xenografts
dc.creator.none.fl_str_mv Monterrubio, Carles
Paco, Sonia
Vila Ubach, Mónica
Rodríguez, Eva
Glisoni, Romina Julieta
Lavarino, Cinzia
Schaiquevich, Paula Susana
Sosnik, Alejandro
Mora, Jaume
Carcaboso, Ángel M.
author Monterrubio, Carles
author_facet Monterrubio, Carles
Paco, Sonia
Vila Ubach, Mónica
Rodríguez, Eva
Glisoni, Romina Julieta
Lavarino, Cinzia
Schaiquevich, Paula Susana
Sosnik, Alejandro
Mora, Jaume
Carcaboso, Ángel M.
author_role author
author2 Paco, Sonia
Vila Ubach, Mónica
Rodríguez, Eva
Glisoni, Romina Julieta
Lavarino, Cinzia
Schaiquevich, Paula Susana
Sosnik, Alejandro
Mora, Jaume
Carcaboso, Ángel M.
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Microdialysis
Oncology
Drug Distribution
Drug Penetration
Hydrophobic Anticancer Drugs
Microdialysis
Neuroblastoma
Patient-Derived Xenograft (Pdx)
Sn-38
Solid Tumor
Steady State
Tumor Homogenate
Tumor Microenvironment
topic Microdialysis
Oncology
Drug Distribution
Drug Penetration
Hydrophobic Anticancer Drugs
Microdialysis
Neuroblastoma
Patient-Derived Xenograft (Pdx)
Sn-38
Solid Tumor
Steady State
Tumor Homogenate
Tumor Microenvironment
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv PURPOSE: To develop a reproducible microdialysis-tumor homogenate method for the study of the intratumor distribution of a highly hydrophobic anticancer drug (SN-38; 7-ethyl-10-hydroxycamptothecin) in neuroblastoma patient-derived xenografts. METHODS: We studied the nonspecific binding of SN-38 to the microdialysis tubing in the presence of 2-hydroxypropyl-beta-cyclodextrin (HPBCD) in the perfusate. We calibrated the microdialysis probes by the zero flow rate (ZFR) method and calculated the enhancement factor (f = extrapolated SN-38 concentration at the ZFR / SN-38 concentration in the dialysed solution) of HPBCD. We characterized the extravasation of HPBCD to tumors engrafted in mice. In vivo microdialysis and terminal homogenate data at the steady state (subcutaneous pump infusions) were used to calculate the volume of distribution of unbound SN-38 (Vu,tumor) in neuroblastoma. RESULTS: HPBCD (10% w/v) in the perfusate prevented the nonspecific binding of SN-38 to the microdialysis probe and enhanced SN-38 recovery (f = 1.86). The extravasation of HPBCD in the tumor during microdialysis was lower than 1%. Vu,tumor values were above 3 mL/g tumor for both neuroblastoma models and suggested efficient cellular penetration of SN-38. CONCLUSIONS: The method contributes to overcome the limitations of the microdialysis technique in hydrophobic drugs and provides a powerful tool to characterize compartmental anticancer drug distribution in xenografts.
Fil: Monterrubio, Carles. Hospital Sant Joan de Déu Barcelona; España. Fundació Sant Joan de Déu; España
Fil: Paco, Sonia. Hospital Sant Joan de Déu Barcelona; España. Fundació Sant Joan de Déu; España
Fil: Vila Ubach, Mónica. Hospital Sant Joan de Déu Barcelona; España. Fundació Sant Joan de Déu; España
Fil: Rodríguez, Eva. Hospital Sant Joan de Déu Barcelona; España. Fundació Sant Joan de Déu; España
Fil: Glisoni, Romina Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina
Fil: Lavarino, Cinzia. Technion - Israel Institute of Technology; Israel
Fil: Schaiquevich, Paula Susana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina
Fil: Sosnik, Alejandro. Hospital Sant Joan de Déu Barcelona; España. Fundació Sant Joan de Déu; España
Fil: Mora, Jaume. Hospital Sant Joan de Déu Barcelona; España. Fundació Sant Joan de Déu; España
Fil: Carcaboso, Ángel M.. Hospital Sant Joan de Déu Barcelona; España. Fundació Sant Joan de Déu; España
description PURPOSE: To develop a reproducible microdialysis-tumor homogenate method for the study of the intratumor distribution of a highly hydrophobic anticancer drug (SN-38; 7-ethyl-10-hydroxycamptothecin) in neuroblastoma patient-derived xenografts. METHODS: We studied the nonspecific binding of SN-38 to the microdialysis tubing in the presence of 2-hydroxypropyl-beta-cyclodextrin (HPBCD) in the perfusate. We calibrated the microdialysis probes by the zero flow rate (ZFR) method and calculated the enhancement factor (f = extrapolated SN-38 concentration at the ZFR / SN-38 concentration in the dialysed solution) of HPBCD. We characterized the extravasation of HPBCD to tumors engrafted in mice. In vivo microdialysis and terminal homogenate data at the steady state (subcutaneous pump infusions) were used to calculate the volume of distribution of unbound SN-38 (Vu,tumor) in neuroblastoma. RESULTS: HPBCD (10% w/v) in the perfusate prevented the nonspecific binding of SN-38 to the microdialysis probe and enhanced SN-38 recovery (f = 1.86). The extravasation of HPBCD in the tumor during microdialysis was lower than 1%. Vu,tumor values were above 3 mL/g tumor for both neuroblastoma models and suggested efficient cellular penetration of SN-38. CONCLUSIONS: The method contributes to overcome the limitations of the microdialysis technique in hydrophobic drugs and provides a powerful tool to characterize compartmental anticancer drug distribution in xenografts.
publishDate 2014
dc.date.none.fl_str_mv 2014-03
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/11336/33112
Schaiquevich, Paula Susana; Sosnik, Alejandro; Monterrubio, Carles; Carcaboso, Ángel M.; Lavarino, Cinzia; Rodríguez, Eva; et al.; Combined Microdialysis-Tumor Homogenate Method for the Study of the Steady State Compartmental Distribution of a Hydrophobic Anticancer Drug in Patient-Derived Xenografts; Springer; Pharmaceutical Research; 32; 9; 3-2014; 2889-2900
0724-8741
1573-904X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/33112
identifier_str_mv Schaiquevich, Paula Susana; Sosnik, Alejandro; Monterrubio, Carles; Carcaboso, Ángel M.; Lavarino, Cinzia; Rodríguez, Eva; et al.; Combined Microdialysis-Tumor Homogenate Method for the Study of the Steady State Compartmental Distribution of a Hydrophobic Anticancer Drug in Patient-Derived Xenografts; Springer; Pharmaceutical Research; 32; 9; 3-2014; 2889-2900
0724-8741
1573-904X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1007/s11095-015-1671-9
info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007/s11095-015-1671-9
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 Springer
publisher.none.fl_str_mv Springer
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 13.13397

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