Institute of Pharmaceutical Technology, Goethe-University, Frankfurt, Germany.
PLoS One. 2011 May 6;6(5):e19121. doi: 10.1371/journal.pone.0019121.
Chemotherapy of glioblastoma is largely ineffective as the blood-brain barrier (BBB) prevents entry of most anticancer agents into the brain. For an efficient treatment of glioblastomas it is necessary to deliver anti-cancer drugs across the intact BBB. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles coated with poloxamer 188 hold great promise as drug carriers for brain delivery after their intravenous injection. In the present study the anti-tumour efficacy of the surfactant-coated doxorubicin-loaded PLGA nanoparticles against rat glioblastoma 101/8 was investigated using histological and immunohistochemical methods.
The particles were prepared by a high-pressure solvent evaporation technique using 1% polyvinylalcohol (PLGA/PVA) or human serum albumin (PLGA/HSA) as stabilizers. Additionally, lecithin-containing PLGA/HSA particles (Dox-Lecithin-PLGA/HSA) were prepared. For evaluation of the antitumour efficacy the glioblastoma-bearing rats were treated intravenously with the doxorubicin-loaded nanoparticles coated with poloxamer 188 using the following treatment regimen: 3 × 2.5 mg/kg on day 2, 5 and 8 after tumour implantation; doxorubicin and poloxamer 188 solutions were used as controls. On day 18, the rats were sacrificed and the antitumour effect was determined by measurement of tumour size, necrotic areas, proliferation index, and expression of GFAP and VEGF as well as Isolectin B4, a marker for the vessel density.
The results reveal a considerable anti-tumour effect of the doxorubicin-loaded nanoparticles. The overall best results were observed for Dox-Lecithin-PLGA/HSA. These data demonstrate that the poloxamer 188-coated PLGA nanoparticles enable delivery of doxorubicin across the blood-brain barrier in the therapeutically effective concentrations.
由于血脑屏障（BBB）阻止大多数抗癌药物进入大脑，胶质母细胞瘤的化疗效果大多不佳。为了有效地治疗胶质母细胞瘤，有必要将抗癌药物递送到完整的 BBB 中。聚（乳酸-共-乙醇酸）（PLGA）纳米粒子用泊洛沙姆 188 涂层后，在静脉注射后作为脑内递药载体具有很大的潜力。在本研究中，使用组织学和免疫组织化学方法研究了表面活性剂包被的阿霉素负载 PLGA 纳米粒子对大鼠胶质母细胞瘤 101/8 的抗肿瘤功效。
通过高压溶剂蒸发技术使用 1%聚乙烯醇（PLGA/PVA）或人血清白蛋白（PLGA/HSA）作为稳定剂制备颗粒。此外，还制备了含有卵磷脂的 PLGA/HSA 颗粒（Dox-Lecithin-PLGA/HSA）。为了评估抗肿瘤功效，用泊洛沙姆 188 包被的载阿霉素纳米粒子对荷瘤大鼠进行静脉内治疗，采用以下治疗方案：肿瘤植入后第 2、5 和 8 天，静脉内给予 3×2.5mg/kg；阿霉素和泊洛沙姆 188 溶液作为对照。第 18 天，处死大鼠，通过测量肿瘤大小、坏死面积、增殖指数以及 GFAP 和 VEGF 的表达，以及作为血管密度标志物的 Isolectin B4，来确定抗肿瘤效果。
结果表明，载阿霉素纳米粒子具有相当大的抗肿瘤作用。Dox-Lecithin-PLGA/HSA 的总体效果最佳。这些数据表明，泊洛沙姆 188 包被的 PLGA 纳米粒子能够以治疗有效的浓度将阿霉素递送到血脑屏障中。
