School of Biomedical Engineering and Imaging, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Biomaterials. 2010 May;31(14):4157-66. doi: 10.1016/j.biomaterials.2010.01.139. Epub 2010 Feb 24.
We report here the development of a chitosan/beta-glycerophosphate(Ch/beta-GP) 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).
我们在此报告了一种壳聚糖/β-甘油磷酸(Ch/beta-GP)温敏凝胶的开发,用于输送鞣花酸(EA)进行癌症治疗。研究了 Ch/beta-GP 凝胶的化学结构、表面形态和粘弹性等特性。考察了载 EA 的 Ch/beta-GP 凝胶的体外 EA 释放率和壳聚糖降解率。通过检测细胞活力,评估了载 EA 的 Ch/beta-GP 凝胶对脑癌细胞(人 U87 神经胶质瘤和大鼠 C6 神经胶质瘤细胞)的抗肿瘤作用。通过 MTS 测定法监测细胞数量和活性。Ch/beta-GP 溶液在体温下形成热诱导凝胶,凝胶化温度和时间受 Ch/beta-GP 溶液最终 pH 的影响。溶菌酶使 EA 的释放速率提高了 2.5 倍,而不存在溶菌酶时的释放速率则提高了 2.5 倍。终 pH 为 6.3 的透析壳聚糖溶液大大减少了形成凝胶所需的β-GP,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,含有 1%(w/v)鞣花酸的壳聚糖凝胶在孵育 3 天时显著降低了 U87 细胞和 C6 细胞的活力(p<0.01 和 p<0.001)。