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OALib Journal期刊
ISSN: 2333-9721
费用：99美元
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pH和还原性双响应性壳聚糖纳米粒子作为药物传输载体
DOI: 10.11777/j.issn1000-3304.2015.14171, PP. 65-71
Keywords: 壳聚糖,二硫键,阿霉素,还原响应性,pH-响应性
Abstract:
用硫辛酸修饰壳聚糖并制备纳米粒子,用催化量的二硫苏糖醇(DTT)处理得到二硫键交联的壳聚糖纳米粒子.二硫键结构的引入不仅使纳米粒子具有还原相应性,而且还引入疏水基团,疏水性的抗癌药阿霉素和荧光探针荧光素通过疏水作用负载于纳米粒子内.二硫交联结构的形成使负载的阿霉素在没有还原剂的环境中(模拟血液的低还原环境)的释放速率大大减慢,而在10mmol/LDTT(模拟细胞内高浓度谷胱甘肽环境)存在下,交联纳米粒子负载的阿霉素快速释放,这可归因于DTT还原二硫键使交联结构破坏.流式细胞实验表明,当介质的pH值由7.4(血液和正常组织pH值)降低到7.0、6.8和6.5(模拟肿瘤组织的微酸性环境)时,交联纳米粒子进入细胞的倾向逐渐增加,这是由于在中性环境中纳米粒子表面是电中性和亲水性的,而在酸性介质中,氨基的质子化使纳米粒子表面带正电荷,zeta电位数据证实这种推断.细胞毒性实验表明,在pH6.5的环境中负载阿霉素的交联纳米粒子对HeLa细胞的毒性大于在pH7.4时的毒性.
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