Convection-Enhanced Delivery of Carboplatin PLGA Nanoparticles for the Treatment of Glioblastoma

被引：68

作者：

Arshad, Azeem ^{[1
]}

Yang, Bin ^{[3
]}

Bienemann, Alison S. ^{[1
]}

Barua, Neil U. ^{[1
]}

Wyatt, Marcella J. ^{[1
]}

Woolley, Max ^{[2
]}

Johnson, Dave E. ^{[2
]}

Edler, Karen J. ^{[3
]}

Gill, Steven S. ^{[1
]}

机构：

[1] Univ Bristol, Sch Clin Sci, Funct Neurosurg Res Grp, Bristol, Avon, England

[2] Renishaw Plc, Neurol Applicat Div, London, Glos, England

[3] Univ Bath, Dept Chem, Bath BA2 7AY, Avon, England

来源：

PLOS ONE | 2015年 / 10卷 / 07期

基金：

英国医学研究理事会;

关键词：

MALIGNANT GLIOMA; GLIADEL WAFERS; BRAIN; DRUG; RELEASE; TRIAL; FLOW;

D O I：

10.1371/journal.pone.0132266

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：16

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