title: Convection-Enhanced Delivery of Carboplatin PLGA Nanoparticles for the Treatment of Glioblastoma.
abstract: 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.
authors.affiliation: Functional Neurosurgery Research Group, School of Clinical Sciences, Bristol University, Bristol, United Kingdom.
authors.forename: Azeem
authors.initials: A
authors.lastname: Arshad
authors.affiliation: Department of Chemistry, University of Bath, Bath, United Kingdom.
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.affiliation: Functional Neurosurgery Research Group, School of Clinical Sciences, Bristol University, Bristol, United Kingdom.
authors.forename: Alison S
authors.initials: AS
authors.lastname: Bienemann
authors.affiliation: Functional Neurosurgery Research Group, School of Clinical Sciences, Bristol University, Bristol, United Kingdom.
authors.forename: Neil U
authors.initials: NU
authors.lastname: Barua
authors.affiliation: Functional Neurosurgery Research Group, School of Clinical Sciences, Bristol University, Bristol, United Kingdom.
authors.forename: Marcella J
authors.initials: MJ
authors.lastname: Wyatt
authors.affiliation: Neurological Applications Division, Renishaw Plc, Gloucestershire, United Kingdom.
authors.forename: Max
authors.initials: M
authors.lastname: Woolley
authors.affiliation: Neurological Applications Division, Renishaw Plc, Gloucestershire, United Kingdom.
authors.forename: Dave E
authors.initials: DE
authors.lastname: Johnson
authors.affiliation: Department of Chemistry, University of Bath, Bath, United Kingdom.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Edler
authors.affiliation: Functional Neurosurgery Research Group, School of Clinical Sciences, Bristol University, Bristol, United Kingdom.
authors.forename: Steven S
authors.initials: SS
authors.lastname: Gill
mesh_terms: D000818:Animals; D016190:Carboplatin / Q000627:therapeutic use*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018481:Convection; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D009498:Neurotoxins / Q000633:toxicity; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D017208:Rats, Wistar; D034421:Sus scrofa
chemical_list: D009498:Neurotoxins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D016190:Carboplatin