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

MONTERRUBIO C; PASCUAL-PASTO G; CANO F; VILA-UBACH M; MANZANARES A; SCHAIQUEVICH P; TORNERO JA; SOSNIK A; MORA J; CARCABOSO AM

BIOMATERIALS

ELSEVIER SCI LTD

Lugar: Amsterdam; Año: 2016 vol. 79 p. 69 - 78

0142-9612

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.