Novel drug delivery system using thermoreversible gelation polymer for malignant glioma.
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.
Arai
Takao
T
Department of Neurosurgery, Jikei University School of Medicine, Tokyo, Japan. takao-a@jikei.ac.jp
Joki
Tatsuhiro
T
Akiyama
Masaharu
M
Agawa
Miyuki
M
Mori
Yuichi
Y
Yoshioka
Hiroshi
H
Abe
Toshiaki
T
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
D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D004343:Drug Implants; D020100:Hydrogels; D011108:Polymers; D011409:Propylene Glycols; D011092:Polyethylene Glycols; D004317:Doxorubicin