Convection-enhanced delivery of carboplatin PLGA nanoparticles for the treatment of glioblastoma

Azeem Arshad; B. Yang; Alison S. Bienemann; Neil U. Barua; Marcella J. Wyatt; Max Woolley; Dave E. Johnson; Karen J. Edler; Steven S. Gill

doi:10.1371/journal.pone.0132266

Convection-enhanced delivery of carboplatin PLGA nanoparticles for the treatment of glioblastoma

Azeem Arshad, B. Yang, Alison S. Bienemann, Neil U. Barua, Marcella J. Wyatt, Max Woolley, Dave E. Johnson, Karen J. Edler, Steven S. Gill

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	e0132266
Journal	PLoS ONE
Volume	10
Issue number	7
DOIs	https://doi.org/10.1371/journal.pone.0132266
Publication status	Published - 2015 Jul 17
Externally published	Yes

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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.",

author = "Azeem Arshad and B. Yang and Bienemann, {Alison S.} and Barua, {Neil U.} and Wyatt, {Marcella J.} and Max Woolley and Johnson, {Dave E.} and Edler, {Karen J.} and Gill, {Steven S.}",

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AU - Arshad, Azeem

AU - Yang, B.

AU - Bienemann, Alison S.

AU - Barua, Neil U.

AU - Wyatt, Marcella J.

AU - Woolley, Max

AU - Johnson, Dave E.

AU - Edler, Karen J.

AU - Gill, Steven S.

N1 - Publisher Copyright: © 2015 Arshad et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2015/7/17

Y1 - 2015/7/17

N2 - 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.

AB - 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.

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Convection-enhanced delivery of carboplatin PLGA nanoparticles for the treatment of glioblastoma

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