双硒交联智能纳米胶束的制备及其药物释放研究

摘要

以含有羟基的葡聚糖(Dex)和含有羧基的硒辛酸(SA)通过酯化反应得到两亲性聚合物Dex-SA,然后在水中自组装形成具有还原响应性的交联Dex-SA纳米胶束.该纳米胶束呈圆球形,平均粒径为(161±10) nm,多分散指数为0.13,Zeta电位为(-20.3±1.4) mV,负载阿霉素(DOX)后的载药率和包封率分别为10.4%和58.9%.药物释放实验表明,交联Dex-SA载药纳米胶束在pH值7.4的10 mmol·L-1PBS溶液中的12 h累计释放率为20.4%,添加10 mmol·L-1 还原型谷胱甘肽(GSH)后的12 h累计释放率可达85.2%.细胞毒性实验表明,交联Dex-SA载药纳米胶束不仅保留了DOX原药本身的高细胞毒性,而且减少了对正常细胞的损伤.交联Dex-SA纳米胶束作为药物载体具有潜在的应用价值.%Through esterification of hydroxyl-containing dextran(Dex) and carboxyl-containing selenooctanoic acid(SA),we synthesized the amphiphilic polymer Dex-SA,which self-assembled to form crosslinked Dex-SA nanomicelle with reduction responsiveness in aqueous solution.The nanomicelle had a spherical shape with average particle size of (161±10) nm,polydispersity index of 0.13,and Zeta potential of (-20.3±1.4) mV.When doxorubicin(DOX) was loaded on the nanomicelle,the drug-loading ratio and entrapment efficiency were 10.4% and 58.9%,respectively.Drug-release experiment showed that the accumulative release rate of DOX-loaded nanomicelle was 20.4% after 12 h in 10 mmol·L-1 PBS(pH value 7.4),which reached 85.2% after adding 10 mmol·L-1 glutathione.Cytotoxicity experiment showed that DOX-loaded nanomicelle not only retained the high cytotoxicity of DOX,but also reduced the damage to normal cells.Therefore,as a drug carrier,the crosslinked Dex-SA nanomicelle has a potential application value.