A chitosan/β-glycerophosphate thermo-sensitive gel for the delivery of ellagic acid for the treatment of brain cancer

A chitosan/β-glycerophosphate thermo-sensitive gel for the delivery of ellagic acid for the treatment of brain cancer
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DOI:
10.1016/j.biomaterials.2010.01.139
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发表时间:
2010-05-01
期刊:
影响因子:
14
通讯作者:
Yang, Yunzhi
Yang, Yunzhi
中科院分区:
工程技术1区
文献类型:
--
作者:
Kim, Sungwoo;Nishimoto, Satoru K.;Yang, Yunzhi

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我们报道了一种壳聚糖/β-甘油磷酸(CH/β-CP)温敏凝胶的开发,以提供用于癌症治疗的鞣花酸(EA)。对CH/β-GP凝胶的化学结构、表面形态和粘弹性进行了表征。考察了EA-CH/β-GP凝胶中EA的体外释放率和壳聚糖的降解率。通过检测细胞活力,评价EA负载的CH/β-GP凝胶对脑癌细胞(人U87胶质母细胞瘤和大鼠C6胶质瘤细胞)的抗肿瘤作用。用MTS法检测细胞数量和活性。CH/β-GP溶液在体温下形成热诱导凝胶,凝胶温度和时间受溶液最终pH值的影响。与不加溶菌酶相比,加入溶菌酶可使EA释放率提高2.5倍。最终pH值为6.3的透析壳聚糖溶液大大降低了凝胶所需的β-糖蛋白,从而显著提高了凝胶的生物相容性(p<0.001)。与壳聚糖凝胶相比,含1%(w/v)鞣花酸的壳聚糖凝胶在孵育3天后,U87细胞和C6细胞的存活率显著降低(p<0.01和p<0.001)。(C)2010爱思唯尔有限公司。保留所有权利。
We report here the development of a chitosan/beta-glycerophosphate(Ch/beta-CP) thermo-sensitive gel to deliver ellagic acid (EA) for cancer treatment. The properties of the Ch/beta-GP gels were characterized regarding chemical structure, surface morphology, and viscoelasticity. In vitro EA release rate from the EA loaded Ch/beta-GP gel and chitosan degradation rate were investigated. The anti-tumor effect of the EA loaded Ch/beta-GP gel on brain cancer cells (human U87 glioblastomas and rat C6 glioma cells) was evaluated by examining cell viability. Cell number and activity were monitored by the MTS assay. The Ch/beta-GP solution formed a heat-induced gel at body temperature, and the gelation temperature and time were affected by the final pH of the Ch/beta-GP solution. The lysozyme increased the EA release rate by 2.5 times higher than that in the absence of lysozyme. Dialyzed chitosan solution with final pH 6.3 greatly reduced the beta-GP needed for gelation, thereby significantly improving the biocompatibility of gel (p < 0.001). The chitosan gels containing 1% (w/v) of ellagic acid significantly reduced viability of U87 cells and C6 cells compared with the chitosan gels at 3 days incubation (p < 0.01, and p < 0.001, respectively). (C) 2010 Elsevier Ltd. All rights reserved.