SN-38-loaded nanofiber matrices for local control of pediatric solid tumors after subtotal resection surgery. (February 2016)

• Record Type: Journal Article
• Authors: Monterrubio, Carles; Pascual-Pasto, Guillem; Cano, Francisco; Vila-Ubach, Monica; Manzanares, Alejandro; Schaiquevich, Paula; Tornero, Jose A.; Sosnik, Alejandro; Mora, Jaume; Carcaboso, Angel M.
• Is Part Of: Biomaterials. Volume 79(2016)
• Page Start: 69
• Page End: 78
• Publication Date: 2016-02
• Subjects: Local chemotherapy delivery -- SN-38 -- Poly(lactic acid) electrospun nanofibers -- Pediatric solid tumor -- Pharmacokinetics -- Microdialysis; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2015.11.055
• Languages: English
• ISSNs: 0142-9612

Abstract

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.