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. 2011 May 6;6(5):e19121.
doi: 10.1371/journal.pone.0019121.

Efficient chemotherapy of rat glioblastoma using doxorubicin-loaded PLGA nanoparticles with different stabilizers

Stefanie Wohlfart  1 , Alexander S Khalansky, Svetlana Gelperina, Olga Maksimenko, Christian Bernreuther, Markus Glatzel, Jörg Kreuter
Affiliations

Efficient chemotherapy of rat glioblastoma using doxorubicin-loaded PLGA nanoparticles with different stabilizers

Stefanie Wohlfart et al. PLoS One. .

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 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.

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Conflict of interest statement

Competing Interests: Although two of the authors (S.G. and O.M.) are employed by a commercial company (Nanosystem LTD.), no patent is pending and these particles are not in a commercial development. This does not alter the authors′ adherence to all the PLoS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. Release of doxorubicin from different types of PLGA nanoparticles stabilized by human serum albumin (water, 37°C, n = 3).
Figure 2
Figure 2. Histological and immunohistochemical evaluation of necrotic areas, proliferation index, GFAP expression, vessel density, and VEGF expression on day 18 after chemotherapy of 101/8 rat glioblastoma with different doxorubicin-PLGA formulations, doxorubicin solution, and poloxamer 188 (P 188) solution as control.
Figure 3
Figure 3. Semi-quantitative analysis of the extent of necrosis after treatment with Dox-PLGA formulations, Dox-sol, and surfactant solution.
See this image and copyright information in PMC

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