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Chemotherapy of glioblastoma in rats using doxorubicin‐loaded nanoparticles
International journal of cancer, 2004-05, Vol.109 (5), p.759-767
Steiniger, Sebastian C.J.
Kreuter, Jörg
Khalansky, Alexander S.
Skidan, Igor N.
Bobruskin, Alexey I.
Smirnova, Zoya S.
Severin, Sergey E.
Uhl, Reiner
Kock, Martin
Geiger, Kathrin D.
Gelperina, Svetlana E.
2004
Volltextzugriff (PDF)
Details
Autor(en) / Beteiligte
Steiniger, Sebastian C.J.
Kreuter, Jörg
Khalansky, Alexander S.
Skidan, Igor N.
Bobruskin, Alexey I.
Smirnova, Zoya S.
Severin, Sergey E.
Uhl, Reiner
Kock, Martin
Geiger, Kathrin D.
Gelperina, Svetlana E.
Titel
Chemotherapy of glioblastoma in rats using doxorubicin‐loaded nanoparticles
Ist Teil von
International journal of cancer, 2004-05, Vol.109 (5), p.759-767
Ort / Verlag
Hoboken: Wiley Subscription Services, Inc., A Wiley Company
Erscheinungsjahr
2004
Quelle
Wiley-Blackwell Journals
Beschreibungen/Notizen
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 in vivo using an animal model created by implantation of 101/8 glioblastoma tumor in rat brains. Groups of 5–8 glioblastoma‐bearing rats (total n = 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.
Sprache
Englisch
Identifikatoren
ISSN: 0020-7136
eISSN: 1097-0215
DOI: 10.1002/ijc.20048
Titel-ID: cdi_proquest_miscellaneous_17926049
Format
–
Schlagworte
Animals
,
Antibiotics, Antineoplastic - administration & dosage
,
Antibiotics, Antineoplastic - adverse effects
,
Antibiotics, Antineoplastic - therapeutic use
,
Brain Neoplasms - drug therapy
,
chemotherapy
,
doxorubicin
,
Doxorubicin - administration & dosage
,
Doxorubicin - adverse effects
,
Doxorubicin - therapeutic use
,
glioblastoma
,
Glioblastoma - drug therapy
,
histology
,
Immunohistochemistry
,
Male
,
nanoparticles
,
Nanotechnology
,
Rats
,
Rats, Wistar
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