efficient chemotherapy of rat glioblastoma using doxorubicin-loaded plga nanoparticles with different stabilizers有效的化疗大鼠胶质母细胞瘤用doxorubicin-loaded plga纳米粒子不同的稳定剂.pdfVIP

Efficient Chemotherapy of Rat Glioblastoma Using Doxorubicin-Loaded PLGA Nanoparticles with Different Stabilizers 1 2 3 3 Stefanie Wohlfart , Alexander S. Khalansky , Svetlana Gelperina , Olga Maksimenko , Christian 4 4 ¨ 1 Bernreuther , Markus Glatzel , Jorg Kreuter * 1 Institute of Pharmaceutical Technology, Goethe-University, Frankfurt, Germany, 2 Institute of Human Morphology, Moscow, Russia, 3 Nanosystem Ltd., Moscow, Russia, 4 Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Abstract 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 us