The effect of AZD2171- or sTRAIL/Apo2L-loaded polylactic-co-glycolic acid microspheres on a subcutaneous glioblastoma model
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| 024 | 7 | 0 | |a 10.1007/s10544-015-9969-2 |2 doi |
| 035 | |a (NATIONALLICENCE)springer-10.1007/s10544-015-9969-2 | ||
| 245 | 0 | 4 | |a The effect of AZD2171- or sTRAIL/Apo2L-loaded polylactic-co-glycolic acid microspheres on a subcutaneous glioblastoma model |h [Elektronische Daten] |c [Anna Shivinsky, Tomer Bronshtein, Tom Haber, Marcelle Machluf] |
| 520 | 3 | |a Studies with AZD2171—a new anti-angiogenic inhibitor of tyrosine kinases associated with VEGF signaling—have shown great promise for treating glioblastoma. Unfortunately, AZD2171 success is limited by low permeability through the blood-brain barrier. Due to AZD2171's short half-life and high toxicity, its local administration will require multiple intracranial procedures, making this approach clinically unfeasible. In this study, we investigated the potential of the highly hydrophobic AZD2171, released from modified polylactic-co-glycolic acid microspheres (PLGA-MS), to treat glioblastoma. To further demonstrate the versatile loading capacity of this system, the same PLGA formulation, which was found optimal for the loading and release of AZD2171, was tested with sTRAIL/Apo2L—a biologic drug that is very different than AZD2171 in its molecular weight, solubility, and charge. AZD2171 released from PLGA-MS was at least effective as the free drug in inhibiting endothelial growth and proliferation (in vitro), and, surprisingly, had a profound cytotoxic effect also towards in vitro cultured glioblastoma cell-lines (U87 and A172). Complete tumor inhibition was achieved following a single treatment with AZD2171-loaded PLGA-MS (6 mg/kg) administered locally adjacent to human U87 glioma tumors inoculated subcutaneously in nude mice. This improved effect, compared to other therapeutic approaches involving AZD2171, was shown to affect both tumor vasculature and the glioma cells. sTRAIL-loaded microspheres, administered at very low doses (0.3 mg/kg), led to 35% inhibition of tumor growth in 2weeks. Collectively, our results provide pre-clinical evidence for the potential of PLGA formulations of AZD2171 and sTRAIL to serve as an effective treatment for glioblastoma. | |
| 540 | |a Springer Science+Business Media New York, 2015 | ||
| 690 | 7 | |a AZD2171 |2 nationallicence | |
| 690 | 7 | |a sTRAIL |2 nationallicence | |
| 690 | 7 | |a Brain/central nervous system cancers |2 nationallicence | |
| 690 | 7 | |a Controlled release |2 nationallicence | |
| 690 | 7 | |a Novel drug delivery systems |2 nationallicence | |
| 690 | 7 | |a PLGA microspheres |2 nationallicence | |
| 700 | 1 | |a Shivinsky |D Anna |u Faculty of Biotechnology and Food Engineering, Technion - Israel Institute of Technology (IIT), 3200003, Haifa, Israel |4 aut | |
| 700 | 1 | |a Bronshtein |D Tomer |u Faculty of Biotechnology and Food Engineering, Technion - Israel Institute of Technology (IIT), 3200003, Haifa, Israel |4 aut | |
| 700 | 1 | |a Haber |D Tom |u Faculty of Biotechnology and Food Engineering, Technion - Israel Institute of Technology (IIT), 3200003, Haifa, Israel |4 aut | |
| 700 | 1 | |a Machluf |D Marcelle |u Faculty of Biotechnology and Food Engineering, Technion - Israel Institute of Technology (IIT), 3200003, Haifa, Israel |4 aut | |
| 773 | 0 | |t Biomedical Microdevices |d Springer US; http://www.springer-ny.com |g 17/4(2015-08-01), 1-15 |x 1387-2176 |q 17:4<1 |1 2015 |2 17 |o 10544 | |
| 856 | 4 | 0 | |u https://doi.org/10.1007/s10544-015-9969-2 |q text/html |z Onlinezugriff via DOI |
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 900 | 7 | |a Metadata rights reserved |b Springer special CC-BY-NC licence |2 nationallicence | |
| 908 | |D 1 |a research-article |2 jats | ||
| 949 | |B NATIONALLICENCE |F NATIONALLICENCE |b NL-springer | ||
| 950 | |B NATIONALLICENCE |P 856 |E 40 |u https://doi.org/10.1007/s10544-015-9969-2 |q text/html |z Onlinezugriff via DOI | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Shivinsky |D Anna |u Faculty of Biotechnology and Food Engineering, Technion - Israel Institute of Technology (IIT), 3200003, Haifa, Israel |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Bronshtein |D Tomer |u Faculty of Biotechnology and Food Engineering, Technion - Israel Institute of Technology (IIT), 3200003, Haifa, Israel |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Haber |D Tom |u Faculty of Biotechnology and Food Engineering, Technion - Israel Institute of Technology (IIT), 3200003, Haifa, Israel |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Machluf |D Marcelle |u Faculty of Biotechnology and Food Engineering, Technion - Israel Institute of Technology (IIT), 3200003, Haifa, Israel |4 aut | ||
| 950 | |B NATIONALLICENCE |P 773 |E 0- |t Biomedical Microdevices |d Springer US; http://www.springer-ny.com |g 17/4(2015-08-01), 1-15 |x 1387-2176 |q 17:4<1 |1 2015 |2 17 |o 10544 | ||