Novel drug delivery system using thermoreversible gelation polymer for malignant glioma
Novel drug delivery system using thermoreversible gelation polymer for malignant glioma
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DOI：
10.1007/s11060-005-9001-4
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发表时间：
2006-03-01
影响因子：
3.9
通讯作者：
Abe, Toshiaki
中科院分区：
文献类型：
--
作者：
Arai, Takao;Joki, Tatsuhiro;Abe, Toshiaki
已经报道了许多局部治疗肿瘤的方法，并证明了它们在恶性胶质瘤患者中的有效性。我们研究了热可逆凝胶聚合物(TGP)作为一种新型的药物释放系统(DDS)来治疗这种类型的肿瘤。TGP在所选择的溶胶-凝胶转变温度以下发生溶胶凝胶转变，即在所选择的溶胶凝胶转变温度以下的溶胶相中是水溶的，在该温度以上的凝胶相中不溶于水。我们将阿霉素与TGP偶联，制备了阿霉素-TGP(DXR-TGP)，并研究了DXR-TGP在体内外的阿霉素释放动力学及抗肿瘤活性。阿霉素在TGP中的扩散速度为9.4×10~(-7)cm~(-2)/S，释放可靠。DXR-TGP对人脑胶质瘤细胞株T98G和U87 MG及裸鼠皮下肿瘤模型均有一定的抗肿瘤活性。病理上，DXR-TGP组增殖标记物Ki-67的检测率明显低于对照组(分别为30-40%和60-70%)。据我们所知，这是TGP作为一种新的药物传递系统的第一次报道，进一步我们提供了TGP作为一种新的DDS治疗恶性胶质瘤的潜力的证据。
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 9.4 x 10(-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.