超过90％的胶质瘤复发出现于瘤腔周边2cm范围内。局部化疗可提高病灶处的药物浓度及作用时间，是防治胶质瘤复发的有效方法。然而，现有局部化疗系统存在引起脑水肿及化疗耐药等问题。肿瘤低氧不仅是胶质瘤抵抗贝伐单抗治疗的重要因素，而且参与介导多种替莫唑胺耐药的分子机制。我们前期筛选并验证了阿苯达唑可有效抑制肿瘤低氧,阿苯达唑低毒高效，是临床上应用多年的抗寄生虫药物。我们拟采用明胶、聚己内酯及聚氧化乙烯，借助三轴电纺丝技术，构建贝伐单抗-阿苯达唑-替莫唑胺新型复合缓释系统，实现对多种药物序贯释放的精确调控：外层贝伐单抗减轻术后脑水肿、阻断残存肿瘤血管生成，提高缓释系统安全性；中层阿苯达唑抑制胶质瘤产生低氧环境，逆转化疗抵抗性；核心层替莫唑胺杀伤肿瘤细胞，三药协同抑制胶质瘤复发。本研究将明确该缓释体系的药物释放曲线、药物配比等技术细节，并验证其在原位胶质瘤动物模型中的安全性及疗效。

More than 90% of gliomas recur within 2cm of the residual cavity. The local chemotherapy system characterized by a higher drug concentration and longer treatment duration in the focal location is a promising therapeutic strategy for glioma patients. However, existing local chemotherapy systems are companied by some disadvantages such as chemoresistance and brain edema. Intratumoral hypoxia not only is an important factor of glioma resistance to bevacizumab (BEV) treatment, but also contributes to several molecular mechanisms mediating temozolomide (TMZ) resistance. As such, we preliminarily screened and verified that albendazole (ABZ) effectively inhibits intratumoral hypoxia. ABZ has a low toxicity and high activity when used as an antihelmintic drug over the decades. We will construct a BEV-ABZ-TMZ composite sustained release chemotherapy system by the tri-co-axial electrospinning technique using gelatin, polycaprolactone, and polyethylene oxide as materials, which results in accurately controlling the time and phase of drugs sequential release. BEV in the outer sheath alleviates brain edema and impairs tumor angiogenesis of the residuals, improving the safety of sustained release chemotherapy system. ABZ in the intermediate layer inhibits the expression of HIF-1α, which overcomes the chemoresistance of gliomas. TMZ in the core is cytotoxic to tumor cells so that glioma recurrence is prevented. In this study, the appropriate drug release curve, the ratio of drugs and other technique details will be determined and the safety and efficacy of this local sustained release chemotherapy system will be validated by an orthotopically implanted glioma model.