von Eckardstein Kajetan L, Patt Stephan, Kratzel Christine, Kiwit Jürgen C W, Reszka Regina
Department of Neurosurgery, HELIOS Klinikum Berlin, Klinikum Buch, Berlin, Hobrechtsfelder Chaussee 96, 13125, Germany.
J Neurooncol. 2005 May;72(3):209-15. doi: 10.1007/s11060-004-3010-6.
Implanted drug carrier systems for retarded chemotherapy against gliomas are mainly based upon polymers containing nitrosoureas. The authors have developed an intracavitary carrier system of biodegradable liquid crystalline cubic phases encapsulating carboplatin and paclitaxel and studied it for release kinetics, antitumor activity, and survival prolongation. A total of 61 Fisher rats with F98 tumors were divided into six treatment groups at day 12 post-inoculation, receiving either no treatment, surgery with partial tumor resection, or partial resection with implantation of cubic phases containing either paclitaxel and carboplatin, paclitaxel alone, carboplatin alone, or no drug. Animals were killed for tumor size analysis at day 21 post-inoculation (n=28) or were included in survival studies (n=33). Additional 12 animals received a paclitaxel/carboplatin application and were killed at different time intervals (6 h, 24 h, 48 h, 5 d, 7 d, 10 d post-agent application) for in vivo diffusion studies. Animals from the paclitaxel/carboplatin group showed a significantly smaller tumor (mean 3.25 mm2+/-SD 1.79 mm2) than animals from the control group (15.30+/-5.86 mm2; P=0.0031), animals having received the empty matrix (11.62+/-6.66 mm2; P=0.0241), and animals after tumor resection without implantation (20.87+/-3.56 mm2; P<or=0.0001). There was no significant difference in survival. Carboplatin was found in brain tissue at 6 h, paclitaxel was found at up to 48 h after implantation at 3 mm distance. Biodegradable crystalline cubic phases embedding cytotoxic drugs as paclitaxel and carboplatin might play an important role in local glioblastoma treatment.
用于延缓性化疗治疗神经胶质瘤的植入式药物载体系统主要基于含亚硝基脲的聚合物。作者开发了一种可生物降解的液晶立方相腔内载体系统，该系统包裹着卡铂和紫杉醇，并对其释放动力学、抗肿瘤活性和生存期延长情况进行了研究。总共61只接种了F98肿瘤的Fisher大鼠在接种后第12天被分为六个治疗组，分别接受不治疗、肿瘤部分切除手术，或部分切除并植入含紫杉醇和卡铂的立方相、仅含紫杉醇的立方相、仅含卡铂的立方相或不含药物的立方相。在接种后第21天处死动物进行肿瘤大小分析（n = 28），或将其纳入生存期研究（n = 33）。另外12只动物接受紫杉醇/卡铂给药，并在不同时间间隔（给药后6小时、24小时、48小时、5天、7天、10天）处死用于体内扩散研究。紫杉醇/卡铂组的动物肿瘤明显小于对照组动物（平均3.25平方毫米±标准差1.79平方毫米）（对照组为15.30±5.86平方毫米；P = 0.0031）、接受空基质的动物（11.62±6.66平方毫米；P = 0.0241）以及肿瘤切除后未植入的动物（20.87±3.56平方毫米；P≤0.0001）。生存期无显著差异。在脑组织中6小时时可检测到卡铂，在植入后3毫米距离处，长达48小时可检测到紫杉醇。嵌入细胞毒性药物如紫杉醇和卡铂的可生物降解结晶立方相可能在局部胶质母细胞瘤治疗中发挥重要作用。
