Novel drug delivery system using thermoreversible gelation polymer for malignant glioma

• Published in: Journal of neuro-oncology 2006-03, Vol.77 (1), p.9-15
• Main Authors: Arai, Takao, Joki, Tatsuhiro, Akiyama, Masaharu, Agawa, Miyuki, Mori, Yuichi, Yoshioka, Hiroshi, Abe, Toshiaki
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - analysis; Antibiotics, Antineoplastic - pharmacokinetics; Diffusion; Doxorubicin - administration & dosage; Doxorubicin - analysis; Doxorubicin - pharmacokinetics; Drug Carriers - administration & dosage; Drug Carriers - chemistry; Drug Carriers - pharmacokinetics; Drug Implants - administration & dosage; Drug Implants - chemistry; Drug Implants - pharmacokinetics; Glioma - drug therapy; Humans; Hydrogels - administration & dosage; Hydrogels - chemistry; Hydrogels - pharmacokinetics; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasms, Experimental - drug therapy; Polyethylene Glycols - administration & dosage; Polyethylene Glycols - chemistry; Polyethylene Glycols - pharmacokinetics; Polymers - administration & dosage; Polymers - chemistry; Polymers - pharmacokinetics; Propylene Glycols - administration & dosage; Propylene Glycols - chemistry; Propylene Glycols - pharmacokinetics; Solubility; Temperature; Tumor Cells, Cultured
• ISSN: 0167-594X; 1573-7373
• DOI: 10.1007/s11060-005-9001-4

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 9.4x10(-7) cm(2)/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.