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

Arshad, Azeem ; Yang, B. ; Bienemann, Alison S. ; Barua, Neil U. ; Wyatt, Marcella J. ; Woolley, Max ; Johnson, Dave E. ; Edler, Karen J. LU orcid and Gill, Steven S. (2015) In PLoS ONE 10(7).
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... (More)

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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author
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publishing date
type
Contribution to journal
publication status
published
in
PLoS ONE
volume
10
issue
7
article number
e0132266
publisher
Public Library of Science (PLoS)
external identifiers
  • pmid:26186224
  • scopus:84940871819
ISSN
1932-6203
DOI
10.1371/journal.pone.0132266
language
English
LU publication?
no
additional info
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.
id
2ce76b30-bc59-4043-bd45-0813d37728af
date added to LUP
2023-03-29 11:46:58
date last changed
2025-07-14 02:20:25
@article{2ce76b30-bc59-4043-bd45-0813d37728af,
  abstract     = {{<p>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.</p>}},
  author       = {{Arshad, Azeem and Yang, B. and Bienemann, Alison S. and Barua, Neil U. and Wyatt, Marcella J. and Woolley, Max and Johnson, Dave E. and Edler, Karen J. and Gill, Steven S.}},
  issn         = {{1932-6203}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{7}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLoS ONE}},
  title        = {{Convection-enhanced delivery of carboplatin PLGA nanoparticles for the treatment of glioblastoma}},
  url          = {{http://dx.doi.org/10.1371/journal.pone.0132266}},
  doi          = {{10.1371/journal.pone.0132266}},
  volume       = {{10}},
  year         = {{2015}},
}