Kooperativer Bibliotheksverbund

Berlin Brandenburg

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  • 1
    Language: English
    In: PLoS ONE, 2011, Vol.6(5), p.e19121
    Description: 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.
    Keywords: Research Article ; Biology ; Medicine ; Immunology ; Oncology
    E-ISSN: 1932-6203
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  • 2
    Language: English
    In: Journal of Controlled Release, 2007, Vol.117(1), pp.51-58
    Description: Poly(butyl cyanoacrylate) nanoparticles coated with poloxamer 188 (Pluronic® F68) and also, as shown previously, polysorbate 80 (Tween® 80) considerably enhance the anti-tumour effect of doxorubicin against an intracranial glioblastoma in rats. The investigation of plasma protein adsorption on the surface of the drug-loaded nanoparticles by two-dimensional electrophoresis (2-D PAGE) revealed that both surfactants, besides other plasma components, induced a considerable adsorption of apolipoprotein A-I (ApoA-I). It is hypothesized that delivery of doxorubicin to the brain by means of nanoparticles may be augmented by the interaction of apolipoprotein A-I that is anchored on the surface of the nanoparticles with the scavenger receptor class B type I (SR-BI) located at the blood–brain barrier. This is the first study that shows a correlation between the adsorption of apolipoprotein A-I on the nanoparticle surface and the delivery of the drug across the blood–brain barrier.
    Keywords: Apolipoprotein A-I ; Chemotherapy ; Glioblastoma ; Nanoparticles ; Poly(Butyl Cyanoacrylate) ; Poloxamer 188 ; Polysorbate 80 ; Rats ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0168-3659
    E-ISSN: 1873-4995
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  • 3
    Language: English
    In: International Journal of Cancer, 01 May 2004, Vol.109(5), pp.759-767
    Description: Glioblastomas belong to the most aggressive human cancers with short survival times. Due to the blood‐brain barrier, they are mostly inaccessible to traditional chemotherapy. We have recently shown that doxorubicin bound to polysorbate‐coated nanoparticles crossed the intact blood‐brain barrier, thus reaching therapeutic concentrations in the brain. Here, we investigated the therapeutic potential of this formulation of doxorubicin using an animal model created by implantation of 101/8 glioblastoma tumor in rat brains. Groups of 5–8 glioblastoma‐bearing rats (total = 151) were subjected to 3 cycles of 1.5–2.5 mg/kg body weight of doxorubicin in different formulations, including doxorubicin bound to polysorbate‐coated nanoparticles. The animals were analyzed for survival (% median increase of survival time, Kaplan‐Meier). Preliminary histology including immunocytochemistry (glial fibrillary acidic protein, ezrin, proliferation and apoptosis) was also performed. Rats treated with doxorubicin bound to polysorbate‐coated nanoparticles had significantly higher survival times compared with all other groups. Over 20% of the animals in this group showed a long‐term remission. Preliminary histology confirmed lower tumor sizes and lower values for proliferation and apoptosis in this group. All groups of animals treated with polysorbate‐containing formulations also had a slight inflammatory reaction to the tumor. There was no indication of neurotoxicity. Additionally, binding to nanoparticles may reduce the systemic toxicity of doxorubicin. This study showed that therapy with doxorubicin bound to nanoparticles offers a therapeutic potential for the treatment of human glioblastoma. © 2004 Wiley‐Liss, Inc.
    Keywords: Nanoparticles ; Doxorubicin ; Glioblastoma ; Chemotherapy ; Histology
    ISSN: 0020-7136
    E-ISSN: 1097-0215
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  • 4
    Language: English
    In: Journal of Nanoneuroscience, 12/01/2009, Vol.1(2), pp.144-151
    Description: Previous investigations have shown that doxorubicin bound to poly(butyl cyanoacrylate) nanoparticles coated with polysorbate 80 (Tween® 80) is able to cross the blood-brain barrier upon intravenous administration and is effective against intracranially implanted 101/8 glioblastoma multiforme in rats at the treatment regimen of 3 × 1.5 mg/kg (as doxorubicin) on days 2, 5, 8 post tumour implantation. The objective of the present study was to investigate the possibility to further prolong the survival of rats with 101/8 glioblastoma by extending the treatment regimen. Doxorubicin-loaded poly(butyl cyanoacrylate) nanoparticles coated with polysorbate 80 were injected using two different therapeutic regimens. Two groups received four injections at the dose of 1.5 mg/kg (as doxorubicin) on days 2, 5, 8, and 16 post tumour implantation and two other groups received an additional injection on day 20 (5 × 1.5 mg/kg). Histological and immunohistochemical analyses were carried out 24 and 30 days after tumour inoculation to assess the effect of the different therapy regimens in comparison to an untreated control group. The results demonstrate that the extended chemotherapy provided an enhanced survival. Comparison of the treatment outcomes revealed that the five-injection regimen produced a more distinctive antitumor effect manifested as a decreased tumour area and proliferation index as well as a decreased necrotic area and a smaller vascular network. Tumour regression was achieved in approximately 40% of the treated animals. These results demonstrate the promising therapeutic potential of doxorubicin-loaded nanoparticles for systemic chemotherapy of human glioblastoma multiforme.
    Keywords: Doxorubicin ; Poly(Butyl Cyanoacrylate) Nanoparticles ; Drug Delivery ; Cancer Chemotherapy ; Glioblastoma ; Histology ; Histology;
    ISSN: 19390637
    E-ISSN: 19390653
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