Abstract A86: Preclinical refinement of a highly-penetrative polymeric nanoparticle drug delivery system for the treatment of glioblastoma multiforme.

Abstract

Abstract Survival statistics for glioblastoma multiforme (GBM) have remained static despite years of research. Two challenges must be overcome to extend survival: drug delivery and resistance to current therapies. Recently, we have developed a highly-penetrative polymeric nanoparticle system capable of being safely delivered to brain parenchyma using convection-enhanced delivery (CED). We have previously shown that this system is capable of protecting and releasing in a controlled manner agents with activity against glioma stem cells (GSCs), significantly improving survival in a rat xenograft model of GSC-derived GBM. We describe here our efforts to further refine this potential therapeutic. First, utilizing high-throughput small molecule screening of a library of generic and FDA- and internationally-approved compounds against GSCs of varying morphologies and genetic composition, we describe the discovery of a novel class of compounds with profound anti-proliferative activity against GSCs but with only very limited activity against normal glial cells. Identified compounds are notably small and lipophilic, making them ideal candidates for translation in our highly-penetrative polymeric nanoparticle system. Second, building upon recent advances in magnetic resonance imaging technology, we describe the incorporation of supraparamagnetic iron oxide (SPIO) in our highly-penetrative polymeric nanoparticle system. We show that incorporation of SPIO does not alter size or in vitro properties of these nanoparticles. Further, we show that SPIO-loaded nanoparticles can be safely delivered to brain parenchyma using CED and can stably release their contents in a controlled fashion over a matter of weeks. These results represent important steps toward clinical application of a promising drug delivery technology. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A86. Citation Format: Garth W. Strohbehn, Komli-Kofi Atsina, Toral R. Patel, Joseph M. Piepmeier, Jiangbing Zhou, W. Mark Saltzman. Preclinical refinement of a highly-penetrative polymeric nanoparticle drug delivery system for the treatment of glioblastoma multiforme. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A86.