SN-38-loaded nanofiber matrices for local control of pediatric solid tumors after subtotal resection surgery
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 ex...
| Autores: | , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2015 |
| País: | España |
| Institución: | Universitat Politècnica de Catalunya (UPC) |
| Repositorio: | UPCommons. Portal del coneixement obert de la UPC |
| Idioma: | inglés |
| OAI Identifier: | oai:upcommons.upc.edu:2117/81791 |
| Acceso en línea: | https://hdl.handle.net/2117/81791 https://dx.doi.org/10.1016/j.biomaterials.2015.11.055 |
| Access Level: | acceso abierto |
| Palabra clave: | Nanofibers Chemotherapy Tumors in children--Chemotherapy Pharmacokinetics Microdialysis--methods Local chemotherapy delivery SN-38 Poly(lactic acid) electrospun nanofibers Pediatric solid tumor Microdialysis Nanofibres Quimioteràpia Farmacocinètica Tumors -- Tractament Àrees temàtiques de la UPC::Enginyeria tèxtil::Teixits::Teixits mèdics Àrees temàtiques de la UPC::Ciències de la salut::Medicina |
| Sumario: | 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 |
|---|