The use of TMZ embedded hydrogels for the treatment of orthotopic human glioma xenografts
The use of TMZ embedded hydrogels for the treatment of orthotopic human glioma xenografts
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DOI：
10.1016/j.jocn.2017.07.027
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发表时间：
2017-11-01
影响因子：
2
通讯作者：
Carter, Bob S.
中科院分区：
文献类型：
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作者：
Adhikari, Bandita;Li, Jie;Carter, Bob S.
目前多形性胶质母细胞瘤(GBM)的治疗受到有效穿越血脑屏障(BBB)的药物的限制。例如，由于血脑屏障和TMZ在生理条件下的不稳定性，全身给药的替莫唑胺(TMZ)只有一小部分可用于治疗。克服这一障碍的一种新方法是绕过血脑屏障，直接将化疗药物局部输送到肿瘤肿块。我们探索了将TMZ负载到一种新型水凝胶基质中，该基质可以液体形式输送，然后在原位固化，并在基质溶解时释放化疗药物。在这里，我们使用胶质母细胞瘤模型测试了180-多赖氨酸和20-多亮氨酸的两亲双嵌段共聚肽水凝胶(K180L20)对TMZ的影响。在体外模型中，我们发现K180L20可以安全地增强TMZ的疗效。该模型包括以神经球悬浮的人胶质母细胞瘤GSC系的治疗，以及体内原位胶质瘤异种鼠模型的治疗。这项技术可能提供了在胶质瘤切除后的腔内衬上一层缓释TMZ的机会，并有可能减少复发。未来需要对更大的动物进行研究来描述这种影响。(C)爱思唯尔有限公司发布的2017年。
The current treatment of glioblastoma multiforme (GBM) is limited by the restricted arsenal of agents which effectively cross the blood brain barrier (BBB). For example, only a fraction of temozolomide (TMZ) administered systemically is available for therapeutic effect because of the BBB and the instability of TMZ under physiologic conditions. A novel approach to overcome this obstacle is to bypass the BBB and locally deliver chemotherapeutic agents directly to the tumor mass. We have explored the loading of TMZ into a novel hydrogel matrix, which can be delivered in liquid form and then solidifies in situ and releases chemotherapy as the matrix dissolves. Here, we tested the effect of amphiphilic diblock copolypeptide hydrogels (DCHs) of 180-poly-lysine and 20-poly-leucine (K180L20) on TMZ using Glioblastoma models. In both the in vitro model, which involved treatment of a human glioblastoma GSC line suspended as neurospheres, and in vivo using an orthotopic glioma xenpgraft mouse model, we found that K180L20 could safely enhance the efficacy of TMZ. This technique may offer the opportunity to 'coat' the inner lining of the cavity following glioma resection with a slow-release TMZ and potentially decrease recurrence. Future studies in larger animals are needed to delineate this effect. (C) 2017 Published by Elsevier Ltd.