P56CONVECTION-ENHANCED DELIVERY (CED) OF CARBOPLATIN NANOSPHERES FOR THE TREATMENT OF GLIOBLASTOMA

INTRODUCTION: We are currently investigating CED of the platinum-based drug, carboplatin as a novel treatment strategy for high grade glioma in adults and children. Although initial results show significant promise, our current treatment strategy requires intermittent infusions due to rapid clearance of carboplatin from the brain. Furthermore, carboplatin is not specifically toxic to tumour cells and has been associated with neurotoxicity at high infused concentrations. We sought to encapsulate carboplatin in lactic acid-glycolic acid copolymer (PLGA) to develop a novel drug delivery system with improved safety and persistence within the brain and increased cancer cytotoxicity. METHOD: We compared the neuronal and tumour cytotoxicity of free carboplatin with encapsulated carboplatin in primary neuronal and GBM cultures. We studied distribution, tissue clearance and toxicity of carboplatin nanospheres following intrastriatal CED in rats. RESULTS: Encapsulation of carboplatin in PLGA nanospheres conferred greater tumour cytotoxicity, reduced neuronal toxicity and prolonged tissue half-life compared with the free drug. CONCLUSION: Encapsulation of carboplatin in PLGA onfers increased safety, with significant increases in tumour cytotoxicity and persistence within the brain. Further investigation is required to determine the translational potential of using PLGA encapsulated-carboplatin as a novel anti-glioma treatment strategy.