Kumar Naraharisetti Pavan, Yung Sheng Ong Benjamin, Wei Xie Jing, Kam Yiu Lee Timothy, Wang Chi-Hwa, Sahinidis Nikolaos V
Molecular Engineering of Biological and Chemical Systems, Singapore-MIT Alliance, Singapore 117576, Singapore.
Biomaterials. 2007 Feb;28(5):886-94. doi: 10.1016/j.biomaterials.2006.09.044. Epub 2006 Oct 25.
Drug-releasing implants delivering chemotherapeutic and radio-sensitizing agents are beginning to play a major role in the post-surgical eradication of residual glioma in the brain. Benefits from early arresting of tumor growth and tumor recovery dynamics stress the impact of drug release profiles of the implants on the efficacy of the treatment. This paper examines responses of BALB/c nude mice, bearing C6 glioma tumors subcutaneously, to treatments by PLGA microspheres, microparticles and discs-delivering Paclitaxel and Etanidazole. The experimental results are used to correlate the efficacy of treatment to in vitro release profiles from the various formulations. Our study demonstrates that radio-sensitizing effects during irradiation could be achieved by double burst profiles from Etanidazole-loaded discs, when compared to controls 17 days after implantation despite the short half-life of Etanidazole (1.4h) in vivo. These results also showed inhibited tumor growth on tumor volumes of 59%, 65% and 70% over the blank placebo groups after 21 days of tumor growth for spray-dried microspheres, electrohydrodynamic atomization microparticles and spray-dried discs, respectively.
释放化疗和放射增敏剂的植入物开始在术后根除脑部残留胶质瘤中发挥重要作用。早期抑制肿瘤生长和肿瘤恢复动态所带来的益处凸显了植入物药物释放曲线对治疗效果的影响。本文研究了皮下接种C6胶质瘤肿瘤的BALB/c裸鼠对聚乳酸-羟基乙酸共聚物（PLGA）微球、微粒和载有紫杉醇及依他硝唑的圆盘治疗的反应。实验结果用于将治疗效果与各种制剂的体外释放曲线相关联。我们的研究表明，尽管依他硝唑在体内半衰期较短（1.4小时），但与对照组相比，植入17天后，载有依他硝唑的圆盘的双脉冲释放曲线可在照射期间实现放射增敏效果。这些结果还显示，在肿瘤生长21天后，喷雾干燥微球、电液动力雾化微粒和喷雾干燥圆盘分别比空白安慰剂组的肿瘤体积抑制率达到59%、65%和70%。
