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Journal of Neuro-Oncology (2006) 77: 915 Springer 2005
DOI 10.1007/s11060-005-9001-4Laboratory InvestigationNovel drug delivery system using thermoreversible gelation polymer for malignant gliomaTakao Arai1 Tatsuhiro Joki1 Masaharu Akiyama2 Miyuki Agawa3 Yuichi Mori4 Hiroshi Yoshioka4 and Toshiaki
Abe11Department of Neurosurgery, Jikei University School of Medicine, Tokyo, Japan;2Department of Pediatrics, Jikei
University School of Medicine, Tokyo, Japan;3Institute of DNA Medicine, Jikei University School of Medicine,
Tokyo, Japan;4Advanced Research Center for Science and Engineering, Waseda University, Tokyo, JapanKey words: doxorubicin, local chemotherapy, malignant glioma, thermoreversible gelation polymerSummaryMany approaches to local tumor treatment have been reported and their ecacy 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 solgel 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 doxorubicinTGP (DXRTGP), then studied the kinetics of doxorubicin release from TGP and
the antitumor activity of DXRTGP in vitro and in vivo. The diusive speed of doxorubicin from TGP was9.4 10)7 cm2/s and doxorubicin was reliably released from TGP. DXRTGP 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 DXRTGP group than in the control group
(3040% vs. 6070%, respectively). This is to the best of our knowledge the rst 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.IntroductionMalignant brain tumor treatment modalities consist of
surgery, radiation and chemotherapy [16]. Regardless
of modality, such tumors tend to recur within centimeters of their origin [7]. Median survival time in patients
with malignant glioma, especially glioblastoma multiforme is less than 1 year, making it important to control
postoperative local recurrence. Chemotherapy is one of
the adjuvant therapies for malignant glioma, but its
ecacy is still controversial due to factors limiting its
eectiveness such as the bloodbrain barrier (BBB),
which restricts the penetration of chemotherapeutic
agents given systemically [8]. Delivery of chemotherapeutic agents directly to tumor sites can overcome these
limitations, and thus recent...