title: Novel drug delivery system using thermoreversible gelation polymer for malignant glioma.
abstract: 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.
authors.affiliation: Department of Neurosurgery, Jikei University School of Medicine, Tokyo, Japan. takao-a@jikei.ac.jp
authors.forename: Takao
authors.initials: T
authors.lastname: Arai
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Joki
authors.forename: Masaharu
authors.initials: M
authors.lastname: Akiyama
authors.forename: Miyuki
authors.initials: M
authors.lastname: Agawa
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Mori
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yoshioka
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Abe
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics; D004058:Diffusion; D004317:Doxorubicin / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D004343:Drug Implants / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D020100:Hydrogels / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D011409:Propylene Glycols / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D012995:Solubility; D013696:Temperature; D014407:Tumor Cells, Cultured
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D004343:Drug Implants; D020100:Hydrogels; D011108:Polymers; D011409:Propylene Glycols; D011092:Polyethylene Glycols; D004317:Doxorubicin