SN-38-loaded nanofiber matrices for local control of pediatric solid tumors after subtotal resection surgery
Por:
Monterrubio C, Pascual-Pastó G, Cano F, Vilà-Ubach M, Manzanares-Quintela A, Schaiquevich P, Tornero JA, Sosnik A, Mora J and Carcaboso AM
Publicada:
1 feb 2016
Ahead of Print:
2 dic 2015
Resumen:
In addition to surgery, local tumor control in pediatric oncology requires new treatments as an alternative to radiotherapy. SN-38 is an anticancer drug with proved activity against several pediatric solid tumors including neuroblastoma, rhabdomyosarcoma and Ewing sarcoma. Taking advantage of the extremely low aqueous solubility of SN-38, we have developed a novel drug delivery system (DDS) consisting of matrices made of poly(lactic acid) electrospun polymer nanofibers loaded with SN-38 microcrystals for local release in difficult-to-treat pediatric solid tumors. To model the clinical scenario, we conducted extensive preclinical experiments to characterize the biodistribution of the released SN-38 using microdialysis sampling in vivo. We observed that the drug achieves high concentrations in the virtual space of the surgical bed and penetrates a maximum distance of 2 mm within the tumor bulk. Subsequently, we developed a model of subtotal tumor resection in clinically relevant pediatric patient derived xenografts and used such models to provide evidence of the activity of the SN-38 DDS to inhibit tumor regrowth. We propose that this novel DDS could represent a potential future strategy to avoid harmful radiation therapy as a primary tumor control together with surgery. (C) 2015 Elsevier Ltd. All rights reserved.
Filiaciones:
Monterrubio C:
Preclinical Therapeutics and Drug Delivery Research Program, Developmental Tumor Biology Laboratory, Fundació Sant Joan de Déu, Santa Rosa 39-57, Esplugues de Llobregat, 08950, Barcelona, Spain
Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Déu Barcelona, Passeig Sant Joan de Déu 2, Esplugues de Llobregat, 08950, Barcelona, Spain
Pascual-Pastó G:
Preclinical Therapeutics and Drug Delivery Research Program, Developmental Tumor Biology Laboratory, Fundació Sant Joan de Déu, Santa Rosa 39-57, Esplugues de Llobregat, 08950, Barcelona, Spain
Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Déu Barcelona, Passeig Sant Joan de Déu 2, Esplugues de Llobregat, 08950, Barcelona, Spain
Cano F:
Institut de Investigació Tèxtil i Cooperació Industrial de Terrassa (INTEXTER), Universitat Politecnica de Catalunya, Colom 15, Terrassa, 08222, Barcelona, Spain
Vilà-Ubach M:
Preclinical Therapeutics and Drug Delivery Research Program, Developmental Tumor Biology Laboratory, Fundació Sant Joan de Déu, Santa Rosa 39-57, Esplugues de Llobregat, 08950, Barcelona, Spain
Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Déu Barcelona, Passeig Sant Joan de Déu 2, Esplugues de Llobregat, 08950, Barcelona, Spain
Manzanares-Quintela A:
Preclinical Therapeutics and Drug Delivery Research Program, Developmental Tumor Biology Laboratory, Fundació Sant Joan de Déu, Santa Rosa 39-57, Esplugues de Llobregat, 08950, Barcelona, Spain
Department of Pediatric Surgery, Hospital Sant Joan de Déu Barcelona, Passeig Sant Joan de Déu 2, Esplugues de Llobregat, 08950, Barcelona, Spain
Schaiquevich P:
CONICET-Clinical Pharmacokinetics Unit, Hospital de Pediatr?a JP Garrahan, Combate de los Pozos 1881, 1245, Buenos Aires, Argentina
Tornero JA:
Cebiotex Biomedical Nanofibers, Parc Cientific de Barcelona, Baldiri i Reixac 4, 08028, Barcelona, Spain
Sosnik A:
Department of Materials Science and Engineering, Technion-Israel Institute of Technology, Technion City, Haifa, Israel
Russell Berrie Nanotechnology Institute (RBNI), Technion-Israel Institute of Technology, Technion City, Haifa, Israel
Mora J:
Preclinical Therapeutics and Drug Delivery Research Program, Developmental Tumor Biology Laboratory, Fundació Sant Joan de Déu, Santa Rosa 39-57, Esplugues de Llobregat, 08950, Barcelona, Spain
Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Déu Barcelona, Passeig Sant Joan de Déu 2, Esplugues de Llobregat, 08950, Barcelona, Spain
Carcaboso AM:
Preclinical Therapeutics and Drug Delivery Research Program, Developmental Tumor Biology Laboratory, Fundació Sant Joan de Déu, Santa Rosa 39-57, Esplugues de Llobregat, 08950, Barcelona, Spain
Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Déu Barcelona, Passeig Sant Joan de Déu 2, Esplugues de Llobregat, 08950, Barcelona, Spain.
Green Submitted, Green Published
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