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Treatment
> Mitoxantrone
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Neurosurgery, 59(6):1296-1303, December 2006
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Abstract |
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Treatment
Of Malignant Gliomas With Mitoxantrone-Loaded Poly (Lactide-Co-Glycolide)
Microspheres
Yemisci, Muge M.D., Ph.D.; Bozdag,
Sibel Ph.D.; Cetin, Meltem Ph.D.; Soylemezoglu, Figen M.D.; Capan,
Yilmaz Ph.D.; Dalkara, Turgay M.D., Ph.D.; Vural, Imran Ph.D.
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Objective. Mitoxantrone (MTZ)
has potent in vitro activity against malignant glioma cell lines, but
it cannot be used effectively as a systemic agent for the treatment of
brain tumors because of its poor central nervous system
penetration.
However, MTZ-loaded
poly(lactide-co-glycolide) (PLGA) microspheres may be injected into
the peritumoral area and into tumor tissue to provide effective and
sustained local drug concentrations without causing systemic side
effects.
Methods. Fisher rats were
randomized into three groups.
The first group (n = 9) was concomitantly
implanted with rat glioma (RG2) cells and blank PLGA microspheres.
The second group (n = 6) was implanted
with RG2 cells and MTZ-loaded PLGA microspheres.
The third group (n = 9) was implanted with
RG2 cells, and MTZ-loaded PLGA microspheres were injected into the
same area after 7 days.
Animals were sacrificed on Day 15 or
35.
Tumor volumes were measured after
hematoxylin and eosin staining.
Distribution kinetics of MTZ in the brain
was determined by high-performance liquid chromatography in nine rats
injected with MTZ-loaded microspheres.
Results. The tumor
volumes were 76 +/- 11 and 107 +/- 11 mm3 (mean +/- standard error) on
Days 15 (n = 6) and 35 (n = 3), respectively, in the control
group.
In rats treated with MTZ-loaded
microspheres on Day 7, tumor volumes were significantly reduced to 17
+/- 4 and 23 +/- 2 mm3 on Days 15 (n = 6) and 35 (n = 3),
respectively.
No tumor formation was observed when
glioma cells and MTZ-loaded PLGA microspheres were implanted
concomitantly (n = 6).
No systemic side effects or parenchymal
inflammatory infiltration were observed in either group of rats.
Brain MTZ concentration was highest at the
injection site and declined with time and distance from the injection
site and with time.
Conclusion. These data
demonstrate that MTZ-loaded PLGA microspheres can deliver therapeutic
concentrations of drug to the tumor and prevent glioma growth without
causing side effects.
This treatment method may increase the
efficiency of antineoplastic therapy and positively impact survival.
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Copyright © 2006, Congress of
Neurological Surgeons. All rights reserved.
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Abstract
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