|
Title:
|
SN-38-loaded nanofiber matrices for local control of pediatric solid tumors after subtotal resection surgery
|
|
Author:
|
Monterrubio, Carles; Pascual Pasto, Guillem; Cano Casas, Francesc; Vilà Ubach, Mònica; Manzanares Quintela, Alejandro; Schaiqueviche, Paula; Tornero García, José Antonio; Sosnik, alejandro; Mora Graupera, Jaume; Montero Carcaboso, Ángel
|
|
Other authors:
|
Universitat Politècnica de Catalunya. Institut d'Investigació Tèxtil i Cooperació Industrial de Terrassa; Universitat Politècnica de Catalunya. TECTEX - Grup de Recerca en Tecnologia Tèxtil |
|
Abstract:
|
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 |
|
Abstract:
|
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 |
|
Subject(s):
|
-Àrees temàtiques de la UPC::Enginyeria tèxtil::Teixits::Teixits mèdics
-Àrees temàtiques de la UPC::Ciències de la salut::Medicina
-Nanofibers
-Chemotherapy
-Tumors in children--Chemotherapy
-Pharmacokinetics
-Microdialysis--methods
-Local chemotherapy delivery
-SN-38
-Poly(lactic acid) electrospun nanofibers
-Pediatric solid tumor
-Pharmacokinetics
-Microdialysis
-Nanofibres
-Quimioteràpia
-Farmacocinètica
-Tumors -- Tractament |
|
Rights:
|
|
|
Document type:
|
Article - Submitted version
Article |
|
Share:
|
|
