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

Azeem Arshad, Bin 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 journalArticle

37 Citations (Scopus)

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 languageEnglish
Article numbere0132266
JournalPLoS ONE
Volume10
Issue number7
DOIs
Publication statusPublished - 17 Jul 2015

Fingerprint

drug delivery systems
Convection
Carboplatin
nanoparticles
Glioblastoma
Nanoparticles
cytotoxicity
glycolic acid
toxicity
platinum
neoplasms
neurotoxicity
composite polymers
tissue distribution
lactic acid
prognosis
half life
Tumors
clinical trials
cell culture

Cite this

Arshad, A., Yang, B., Bienemann, A. S., Barua, N. U., Wyatt, M. J., Woolley, M., ... Gill, S. S. (2015). Convection-enhanced delivery of carboplatin PLGA nanoparticles for the treatment of glioblastoma. PLoS ONE, 10(7), [e0132266]. https://doi.org/10.1371/journal.pone.0132266

Convection-enhanced delivery of carboplatin PLGA nanoparticles for the treatment of glioblastoma. / Arshad, Azeem; Yang, Bin; Bienemann, Alison S.; Barua, Neil U.; Wyatt, Marcella J.; Woolley, Max; Johnson, Dave E.; Edler, Karen J.; Gill, Steven S.

In: PLoS ONE, Vol. 10, No. 7, e0132266, 17.07.2015.

Research output: Contribution to journalArticle

Arshad, A, Yang, B, Bienemann, AS, Barua, NU, Wyatt, MJ, Woolley, M, Johnson, DE, Edler, KJ & Gill, SS 2015, 'Convection-enhanced delivery of carboplatin PLGA nanoparticles for the treatment of glioblastoma', PLoS ONE, vol. 10, no. 7, e0132266. https://doi.org/10.1371/journal.pone.0132266
Arshad A, Yang B, Bienemann AS, Barua NU, Wyatt MJ, Woolley M et al. Convection-enhanced delivery of carboplatin PLGA nanoparticles for the treatment of glioblastoma. PLoS ONE. 2015 Jul 17;10(7). e0132266. https://doi.org/10.1371/journal.pone.0132266
Arshad, Azeem ; Yang, Bin ; Bienemann, Alison S. ; Barua, Neil U. ; Wyatt, Marcella J. ; Woolley, Max ; Johnson, Dave E. ; Edler, Karen J. ; Gill, Steven S. / Convection-enhanced delivery of carboplatin PLGA nanoparticles for the treatment of glioblastoma. In: PLoS ONE. 2015 ; Vol. 10, No. 7.
@article{9066465bcca64bdab7eb7194ba573cd3,
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 Bin 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.}",
note = "open access",
year = "2015",
month = "7",
day = "17",
doi = "10.1371/journal.pone.0132266",
language = "English",
volume = "10",
journal = "PLoS ONE",
issn = "1932-6203",
publisher = "Public Library of Science (PLOS)",
number = "7",

}

TY - JOUR

T1 - Convection-enhanced delivery of carboplatin PLGA nanoparticles for the treatment of glioblastoma

AU - Arshad, Azeem

AU - Yang, Bin

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 - open access

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.

UR - http://www.scopus.com/inward/record.url?scp=84940871819&partnerID=8YFLogxK

UR - http://dx.doi.org/10.1371/journal.pone.0132266

U2 - 10.1371/journal.pone.0132266

DO - 10.1371/journal.pone.0132266

M3 - Article

VL - 10

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 7

M1 - e0132266

ER -