目的以不同程度疏水性修饰的γ-聚谷氨酸(γ-PGA)接枝衍生物(PGA-LA)为载体材料,制备载胰岛素(Ins)纳米胶束。方法制备高、中、低3种疏水性修饰度(GD)的PGA-LA,并测定其临界胶束浓度(CMC)。以3种不同GD值的PGA-LA为载体,采用透析法制备载胰岛素纳米胶束并进行表征。采用圆二色谱法考察二甲亚砜(DMSO)对Ins的影响。用考马斯亮蓝G250染色法探讨胶束的形成机理。结果制备3种PGA-LA,其GD值越高,CMC越小,胶束结构越稳定。制备载胰岛素纳米胶束所用的DMSO对胰岛素的二级结构无影响;PGA-LA的GD值越高,纳米胶束内部的疏水作用力越强,纳米胶束的粒径越小,分布越均匀。结论选择GD值为70.23%的PGA-LA为载体材料制备的载胰岛素纳米胶束,粒径较小,其包封率及载药量均较高。
OBJECTIVE To prepare the insulin (Ins) -loaded micelles using γ -glutamic acid (7 -PGA) graft derivatives (PGA- LA) as the carrier materials. METHODS PGA - LA was obtained with different hydrophobic modification degrees (GD values) and the critical micelle concentration (CMC) was measured. Ins -loaded micelles were prepared by dialysis method, and their characterization was studied. Then, circular dichroism (CD) was applied to investigate the effect of DMSO on the secondary structure of Ins and coomassie brilliant blue (CBB) stains were used to investigate the mechanism of micelles formation. RESULTS PGA - LA with higher GD value of 70.23% had smaller CMC value of 0.11 μg·mL^-1. CD spectrum confirmed that DMSO had no influence on the secondary structure of Ins. Then, CBB spectrum confirmed the stronger hydrophobic interaction between Ins and PGA - LA with higher GD value, and it contributed to decreasing the particle size of Ins - loaded micelles. CONCLUSION Ins - loaded micelles prepared with GD value of 70.23% exhibites good particle size and size distribution, as well as high encapsulation efficiency and drug loading.