Convection-Enhanced Delivery of Carboplatin PLGA Nanoparticles for the Treatment of Glioblastoma.
Convection-Enhanced Delivery of Carboplatin PLGA Nanoparticles for the Treatment of Glioblastoma.
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DOI：
10.1371/journal.pone.0132266
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Gill SS
中科院分区：
文献类型：
--
作者：
Arshad A;Yang B;Bienemann AS;Barua NU;Wyatt MJ;Woolley M;Johnson DE;Edler KJ;Gill SS
我们目前使用对流增强递送(CED)的铂类药物卡铂作为成人和儿童高级别胶质母细胞瘤的一种新的治疗策略。尽管初步结果显示，卡铂对肿瘤细胞没有特别的毒性，但在临床前研究中，高浓度的卡铂与神经毒性有关。我们的治疗策略需要间歇性输液，因为卡铂从大脑中迅速清除。本研究将卡铂包裹在乳酸-乙醇酸共聚物(PLGA)中，开发了一种新型的药物释放系统。在原代培养的神经元和胶质母细胞瘤细胞中评估神经元和肿瘤的细胞毒性。卡铂纳米粒在大鼠和猪模型中的分布、组织清除和毒性在CED后进行了评估。卡铂纳米粒具有更强的肿瘤细胞毒性，降低了神经元毒性，延长了组织半衰期。综上所述，该给药系统有可能改善胶质母细胞瘤患者的预后。
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.