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Berlin Brandenburg

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  • Brain Neoplasms
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  • 1
    Language: English
    In: International Journal of Pharmaceutics, 2011, Vol.415(1), pp.244-251
    Description: Glioblastomas belong to the most devastating cancer diseases. For this reason, polysorbate 80 (Tween 80 )-coated poly(isohexyl cyanoacrylate) (PIHCA) (Monorex ) nanoparticles loaded with doxorubicin were developed and tested for their use for the treatment of glioblastomas. The preparation of the nanoparticles resulted in spherical particles with high doxorubicin loading. The physico-chemical properties and the release of doxorubicin from the PIHCA-nanoparticles were analysed, and the influence on cell viability of the rat glioblastoma 101/8-cell line was investigated. In vitro, the empty nanoparticles did not show any toxicity, and the anti-cancer effects of the drug-loaded nanoparticles were increased in comparison to doxorubicin solution, represented by IC values. The in vivo efficacy was then tested in intracranially glioblastoma 101/8-bearing rats. Rats were treated with 3 × 1.5 mg/kg doxorubicin and were sacrificed 18 days after tumour transplantation. Histological and immunohistochemical analyses were carried out to assess the efficacy of the nanoparticles. Tumour size, proliferation activity, vessel density, necrotic areas, and expression of glial fibrillary acidic protein demonstrated that doxorubicin-loaded PIHCA-nanoparticles were much more efficient than the free drug. The results suggest that poly(isohexyl cyanoacrylate) nanoparticles hold great promise for the non-invasive therapy of human glioblastomas.
    Keywords: Doxorubicin ; Nanoparticles ; Poly(Isohexyl Cyanoacrylate) ; Glioblastoma ; Histology ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0378-5173
    E-ISSN: 1873-3476
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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: Drug Delivery, 03 April 2015, Vol.22(3), pp.276-285
    Description: Targeted drug delivery for brain tumor treatment is one of the important objectives in nanomedicine. Human glioblastoma is the most frequent and aggressive type of brain tumors. The preferential expression of membrane protein connexin 43 (Cx43) and brain-specific anion transporter (BSAT1) in the tumor and peritumoral area is a key component for targeted drug delivery. The purpose of this study was to design cisplatin-loaded nanogels conjugated with monoclonal antibodies to Cx43 and BSAT1 for treatment of intracranial gliomas 101/8. MRI volumetric analysis of tumor-bearing rats indicated significantly reduced tumor volume with cisplatin-loaded targeted-nanogel treatment compared to other formulations. The median survival of rats treated with targeted nanogels conjugated with specific mAbs against extracellular loops of Cx43 and BSAT1 were 27 and 26.6 days higher than that in control group, respectively. For the first time we demonstrated the efficiency of mAb-targeted cisplatin-loaded nanogels in the experimental model of glioma 101/8. This approach could facilitate the development of new drug delivery systems for the treatment of gliomas.
    Keywords: Connexin-43 ; Glioblasoma Multiforme ; Monoclonal Antibody ; Nanogels ; Targeted Delivery ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 1071-7544
    E-ISSN: 1521-0464
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  • 4
    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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  • 5
    Language: English
    In: Clinical neuropathology, 2009, Vol.28(3), pp.153-64
    Description: The objective of this study was to investigate the therapeutic effects of doxorubicin bound to polysorbate-coated nanoparticles that had previously been shown to significantly enhance survival in the orthotopic rat 101/8 glioblastoma model. Tumor-bearing animals were subjected to chemotherapy using doxorubicin in solution (Dox-sol) or doxorubicin bound to polysorbate 80-coated poly(butyl cyanoacrylate) nanoparticles (Dox-np) injected intravenously on Days 2, 5 and 8 post tumor implantation. The antitumor effect was assessed on Days 10, 14 and 18 post tumor implantation. Tumors showed signs of malignancy including invasion of brain tissue, brisk mitotic activity, microvascular proliferation, necrosis and increased proliferation resembling human glioblastoma. Dox-np produced a considerably more pronounced antitumor effect exhibited as a reduced tumor size, lower proliferation, and a decreased necrotic area compared to Dox-sol and to untreated control groups. A drastic effect of Dox-np on vascularization indicated an antiangiogenic mode of action.
    Keywords: Drug Delivery Systems ; Angiogenesis Inhibitors -- Administration & Dosage ; Brain Neoplasms -- Drug Therapy ; Doxorubicin -- Administration & Dosage ; Glioblastoma -- Drug Therapy
    ISSN: 0722-5091
    Source: MEDLINE/PubMed (U.S. National Library of Medicine)
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  • 6
    Language: English
    In: Journal of Microencapsulation, 01 January 2006, Vol.23(5), pp.582-592
    Description: Poly(n-butyl cyanoacrylate) nanoparticles coated with polysorbate-80 can enable the transport of bound drugs across the blood-brain barrier (BBB) after i.v. injection. In the present study the influence of different formulation parameters on the anti-tumoural effects of doxorubicin nanoparticles against glioblastoma 101/8 was investigated. The manufacturing parameters of poly(alkyl cyanoacrylate) doxorubicin-loaded nanoparticles were optimized concerning drug loading. The nanoparticles were coated with different surfactants and injected intravenously on days 2, 5 and 8 after intra-cranial implantation of glioblastoma 101/8 to rats. The survival times of all doxorubicin containing preparations, including a doxorubicin solution, increased the survival times significantly compared to untreated tumour-bearing rats. The most pronounced increase in survival was obtained with the poly(n-butyl cyanoacrylate) doxorubicin-loaded nanoparticles coated with polysorbate 80 and 35% of these animals survived for over 180 days (termination of the experiments). The other nanoparticle preparations yielded lower survival times. Poly(n-butyl cyanoacrylate) doxorubicin-loaded nanoparticles coated with polysorbate 80-coated proved to be very efficient against glioblastoma 101/8. The data suggest that the interaction of nanoparticles with the blood after injection as well as the enhanced permeability and retention effect (EPR effect) contributed differently to the anti-tumoural efficacy depending on nanoparticle formulation and surface properties.
    Keywords: Nanoparticles ; Glioblastomas ; Brain Tumours ; Rats ; Poly(N-Butyl Cyanoacrylate) ; Poly(Iso-Butyl Cyanoacrylate) ; Doxorubicin ; Polysorbate 80 ; Poloxamine 908 ; Poloxamer 188 ; Medicine ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0265-2048
    E-ISSN: 1464-5246
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  • 7
    Language: English
    In: Journal of Drug Targeting, 01 January 2006, Vol.14(2), pp.97-105
    Description: It was recently shown that doxorubicin (DOX) bound to polysorbate-coated nanoparticles (NP) crossed the intact blood-brain barrier (BBB), and thus reached therapeutic concentrations in the brain. Here, we investigated the biodistribution in the brain and in the body of poly(butyl-2-cyano[3- 14 C]acrylate) NP ([ 14 C]-PBCA NP), polysorbate 80 (PS 80)-coated [ 14 C]-PBCA NP, DOX-loaded [ 14 C]-PBCA NP in glioblastoma 101/8-bearing rats after i.v. injection. The biodistribution profiles and brain concentrations of radiolabeled NP were determined by radioactivity counting after i.v. administration in rats. Changes in BBB permeability after tumour inoculation were assessed by i.v. injection of Evans Blue solution. The accumulation of NP in the tumour site and in the contralateral hemisphere in glioblastoma bearing-rats probably was augmented by the enhanced permeability and retention effect (EPR effect) that may have been becoming instrumental due to the impaired BBB on the NP delivery into the brain. The uptake of the NP by the organs of the reticuloendothelial system (RES) was reduced after PS 80-coating, but the addition of DOX increased again the concentration of NP in the RES.
    Keywords: Blood-Brain Barrier ; Glioblastoma ; Nanoparticles ; Doxorubicin ; Polysorbate 80 ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 1061-186X
    E-ISSN: 1029-2330
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  • 8
    Language: English
    In: Toxicology Letters, 2002, Vol.126(2), pp.131-141
    Description: Polysorbate 80-coated poly(butyl cyanoacrylate) nanoparticles (NP) were shown to enable the transport of a number of drugs including the anti-tumour antibiotic doxorubicin (DOX) across the blood-brain barrier (BBB) to the brain after intravenous administration and to considerably reduce the growth of brain tumours in rats. The objective of the present study was to evaluate the acute toxicity of DOX associated with polysorbate 80-coated NP in healthy rats and to establish a therapeutic dose range for this formulation in rats with intracranially implanted 101/8 glioblastoma. Single intravenous administration of empty poly(butyl cyanoacrylate) NP in the dose range 100-400 mg/kg did not cause mortality within the period of observation. NP also did not affect body weight or weight of internal organs. Association of DOX with poly(butyl cyanoacrylate) NP did not produce significant changes of quantitative parameters of acute toxicity of the anti-tumour agent. Likewise, the presence of polysorbate 80 in the formulations was not associated with changes in toxicity compared with free or nanoparticulate drug. Dose regimen of 3 x 1.5 mg/kg on days 2, 5, 8 after tumour implantation did not cause drug-induced mortality. The results in tumour-bearing rats were similar to those in healthy rats. These results demonstrate that the toxicity of DOX bound to NP was similar or even lower than that of free DOX.
    Keywords: Doxorubicin ; Glioblastoma ; Nanoparticles ; Poly(Butyl Cyanoacrylate) ; Polysorbate ; Toxicology ; Rats ; Pharmacy, Therapeutics, & Pharmacology ; Public Health
    ISSN: 0378-4274
    E-ISSN: 1879-3169
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