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

Paper ID Volume ID Publish Year Pages File Format Full-Text
5471 389 2016 10 PDF Available
Title
SN-38-loaded nanofiber matrices for local control of pediatric solid tumors after subtotal resection 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.

Keywords
Local chemotherapy delivery; SN-38; Poly(lactic acid) electrospun nanofibers; Pediatric solid tumor; Pharmacokinetics; Microdialysis
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SN-38-loaded nanofiber matrices for local control of pediatric solid tumors after subtotal resection surgery
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 79, February 2016, Pages 69–78
Authors
, , , , , , , , , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us