Novel drug delivery system using thermoreversible gelation polymer for malignant glioma

使用热可逆凝胶聚合物治疗恶性神经胶质瘤的新型药物递送系统

• 批准号: 14571335
• 负责人: JOKI Tatsuhiro
• 金额: $ 2.18万
• 依托单位: The Jikei University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571335/
• 关键词: Brain Tumor; DDS; Local Therapy; Polymer; 局所療法; 選択的COX-2阻害薬; ドキソルビシン; ゲフィニチブ; Drug Delivery System; 温度可変性ポリマー; エンドスタチン; COX-2; アドリアマイシン; NS398

Many approaches to local tumor treatment have been reported and its efficacy demonstrated in patients with malignant glioma. We studied thermoreversible gelation polymer (TGP) as a novel drug delivery system (DDS) in treating this tumor. TGP exhibits sol-gel transition i.e., is water-soluble in the sol phase below the sol-gel transiting temperature which we can set up as we choose 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. Diffusive speed of doxorubicin in from TGP at was 9.4 x 10^<-7> cm^2/sec and doxorubicin was released from TGP whenever DXR-TGP was added. DXR-TGP showed antitumor activity with the human glioma cell lines T98G and U87MG and in a subcutaneous tumor model of nude mice. Pathologically, the proliferation marker MIB-1 labeling of the control group was 60-70% and that of the DXR-TGP group 30-40%. This is to our knowledge, the first report of TGP being applied to DDSs, and this report shows some possibility of using TGP as novel DDS for malignant glioma.

许多肿瘤局部治疗的方法已被报道，其疗效在恶性胶质瘤患者中得到证实。我们研究了热可逆凝胶聚合物（TGP）作为一种新型的药物传递系统（DDS）治疗该肿瘤。TGP表现出溶胶-凝胶转变，即，在低于溶胶-凝胶转变温度（我们可以根据选择设定）时在溶胶相中是水溶性的，而在高于该温度时在凝胶相中是水不溶性的。我们将阿霉素与白芍总苷偶联制备成阿霉素-白芍总苷（DXR-TGP），并研究其体外释药动力学和体内抗肿瘤活性。多柔比星从TGP中的扩散速度为9.4 × 10 - 6 <-7>cm ^2/sec，并且每当加入DXR-TGP时，多柔比星从TGP中释放。DXR-TGP对人胶质瘤细胞株T98 G和U87 MG及裸鼠皮下肿瘤模型均具有抗肿瘤活性。病理学上，对照组增殖标记物MIB-1的标记率为60-70%，DXR-TGP组为30- 40%。据我们所知，这是TGP应用于DDS的首次报道，该报告显示了TGP作为恶性胶质瘤新型DDS的可能性。

项目成果

Novel drug delivery system using thermoreversible gelation polymer for malignant glioma

• DOI: 10.1007/s11060-005-9001-4
• 发表时间: 2006-03-01
• 期刊: JOURNAL OF NEURO-ONCOLOGY
• 影响因子: 3.9
• 作者: Arai, Takao;Joki, Tatsuhiro;Abe, Toshiaki
• 通讯作者: Abe, Toshiaki