Novel drug delivery system using thermoreversible gelation polymer for malignant glioma
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Many approaches to local tumor treatment have been reported and their efficacy demonstrated in patients with malignant glioma. We studied thermoreversible gelation polymer (TGP) as a novel drug delivery system (DDS) for treating this type of tumor. TGP exhibits sol–gel transition i.e., is water-soluble in the sol phase below the chosen sol–gel transiting temperature and water-insoluble in the gel phase above this temperature. We conjugated doxorubicin with TGP to prepare doxorubicin–TGP (DXR–TGP), then studied the kinetics of doxorubicin release from TGP and the antitumor activity of DXR–TGP in vitro and in vivo. The diffusive speed of doxorubicin from TGP was 9.4×10−7 cm2/s and doxorubicin was reliably released from TGP. DXR–TGP showed antitumor activity against the human glioma cell lines T98G and U87MG and in a subcutaneous tumor model in nude mice. Pathologically, detection of the proliferation marker Ki-67 was considerably lower in the DXR–TGP group than in the control group (30–40% vs. 60–70%, respectively). This is to the best of our knowledge the first report of TGP as a novel drug delivery system, and further we provide evidence that TGP exhibits potential for use as a novel DDS for malignant glioma.
Key words:doxorubicin local chemotherapy malignant glioma thermoreversible gelation polymer
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We thank Toshini Okuhara (Division of Surgical Pathology, St. Marianna University School of Medicine Yokohama Seibu Hospital) for preparing paraffin specimens, Dr. Junko Fujigasaki (Division of Neuropathology, Jikei University School of Medicine) for examining specimens, Dr. Yuichi Murayama (Department of Neurosurgery, Jikei University School of Medicine) for their invaluable advice. This work was supported in part by a grant-in-aid for scientific research from the Japan Society for the Promotion of Science (No. 30226378).
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