双硒交联智能纳米胶束的制备及其药物释放研究

Preparation and Drug-Release Behavior of Diselenide-Crosslinked Smart Nanomicelle

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10mmol·L^(-1) PBS溶液中的12h累计释放率为20.4%,添加10mmol·L^(-1)还原型谷胱甘肽(GSH)后的12h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 seleno- octanoic acid（SA）,we synthesized the amphiphilie 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） inV. When doxorubicin（DOX） was loaded on the nanomieelle, 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% af- ter 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.