Convection-Enhanced Delivery of Carboplatin PLGA Nanoparticles for the Treatment of Glioblastoma

• DOI: 10.1371/journal.pone.0132266
• Publication Date: 2015-07-17T18:17:44Z
• Authors: Azeem Arshad; Bin Yang; Alison S. Bienemann; Neil U. Barua; Marcella J. Wyatt; Max Woolley; Dave E. Johnson; Karen J. Edler; Steven S. Gill
• Keywords: Male; 0301 basic medicine; 570; Science; Neurotoxins; Sus scrofa; 610; Convection; Hippocampus; Carboplatin; 03 medical and health sciences; Drug Delivery Systems; Polylactic Acid-Polyglycolic Acid Copolymer; Cell Line, Tumor; Animals; Humans; Lactic Acid; Rats, Wistar; Cells, Cultured; Cell Death; Q; R; Endocytosis; 3. Good health; Medicine; Nanoparticles; Glioblastoma; Polyglycolic Acid; Research Article

We currently use Convection-Enhanced Delivery (CED) of the platinum-based drug, carboplatin as a novel treatment strategy for high grade glioblastoma in adults and children. Although initial results show promise, carboplatin is not specifically toxic to tumour cells and has been associated with neurotoxicity at high infused concentrations in pre-clinical studies. Our treatment strategy requires intermittent infusions due to rapid clearance of carboplatin from the brain. In this study, carboplatin was encapsulated in lactic acid-glycolic acid copolymer (PLGA) to develop a novel drug delivery system. Neuronal and tumour cytotoxicity were assessed in primary neuronal and glioblastoma cell cultures. Distribution, tissue clearance and toxicity of carboplatin nanoparticles following CED was assessed in rat and porcine models. Carboplatin nanoparticles conferred greater tumour cytotoxicity, reduced neuronal toxicity and prolonged tissue half-life. In conclusion, this drug delivery system has the potential to improve the prognosis for patients with glioblastomas.