Efficient Chemotherapy of Rat Glioblastoma Using Doxorubicin-Loaded PLGA Nanoparticles with Different Stabilizers

PLoS One

Alexander S. Khalansky¹  Markus Glatzel²  Christian Bernreuther²  Stefanie Wohlfart³  Jörg Kreuter³  Olga Maksimenko⁴  Svetlana Gelperina⁴ 

[1] Institute of Human Morphology, Moscow, Russia;Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;Institute of Pharmaceutical Technology, Goethe-University, Frankfurt, Germany;Nanosystem Ltd., Moscow, Russia

关键词: Nanoparticles;    Glioblastoma multiforme;    Cancer treatment;    Lecithin;    Histology;    Cancer chemotherapy;    Cell staining;    Intravenous injections;   

DOI  :  10.1371/journal.pone.0019121

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

Background 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. Methodology 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. Conclusion 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.

【 授权许可】

CC BY