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Temozolomide/PLGA microparticles plus vatalanib inhibits tumor growth and angiogenesis in an orthotopic glioma model.

Abstract
Temozolomide (TM) has anti-tumor activity in patients with malignant glioma. Implantable poly (D,L-lactide-co-glycolide) (PLGA) microparticles of TM (TM-MS) have been developed, enhancing the cytotoxicity of TM to Glioma C6 cells. Vatalanib, as anti-angiogenic agent, has also shown anti-tumor activity with malignant gliomas. We examined the combined effects of TM-MS and vatalanib in a rat orthotopic glioma model and found TM-MS offered a greater tumor inhibition than TM, and combination treatment with both of them improved the survival time versus single agent therapy. The combination treatment also demonstrated an inhibition to rat glioma tumors, a significant decrease in cell proliferation, an increase in apoptosis, and a lower microvessel density within the glioma tumors. The results suggest that TM-MS can more effectively inhibit tumor than TM, and combination treatment with TM-MS and vatalanib inhibits tumor growth and angiogenesis and may prove to be a promising therapy for malignant gliomas.
AuthorsYu-Hui Zhang, Zhi-Jian Yue, He Zhang, Gu-Sheng Tang, Yang Wang, Jian-Min Liu
JournalEuropean journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V (Eur J Pharm Biopharm) Vol. 76 Issue 3 Pg. 371-5 (Nov 2010) ISSN: 1873-3441 [Electronic] Netherlands
PMID20816959 (Publication Type: Journal Article)
CopyrightCopyright © 2010 Elsevier B.V. All rights reserved.
Chemical References
  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Phthalazines
  • Pyridines
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • vatalanib
  • Dacarbazine
  • Temozolomide
Topics
  • Angiogenesis Inhibitors (pharmacology, therapeutic use)
  • Animals
  • Antineoplastic Agents (pharmacology, therapeutic use)
  • Antineoplastic Combined Chemotherapy Protocols (pharmacology, therapeutic use)
  • Apoptosis
  • Brain Neoplasms (drug therapy, pathology)
  • Cell Line, Tumor
  • Cell Proliferation (drug effects)
  • Dacarbazine (analogs & derivatives, pharmacology, therapeutic use)
  • Disease Models, Animal
  • Drug Delivery Systems
  • Glioma (drug therapy, pathology)
  • Humans
  • Lactic Acid
  • Male
  • Neovascularization, Pathologic (drug therapy)
  • Phthalazines (pharmacology, therapeutic use)
  • Polyglycolic Acid
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Pyridines (pharmacology, therapeutic use)
  • Rats
  • Rats, Sprague-Dawley
  • Temozolomide
  • Treatment Outcome

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