Key Laboratory of Drug Targeting and Drug Delivery System (Ministry of Education), West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu 610041, China.
Key Laboratory of Drug Targeting and Drug Delivery System (Ministry of Education), West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu 610041, China.
Eur J Pharm Sci. 2018 Jul 1;119:1-12. doi: 10.1016/j.ejps.2018.04.007. Epub 2018 Apr 4.
In this work, we investigated the feasibility of employing metal ion that coordinated with amino group grafted mesoporous silica as a pH-sensitive release carrier of insulin. Mesoporous silica particles were firstly grafted with amino groups. After coordination of metal ions onto the surface of mesoporous pore, insulin was loaded onto mesoporous silica particles through coordination bonds with metal ions. Insulin-loaded mesoporous silica particle with an acid sensitivity between the pH range of physiological environment (pH 7.4) and diabetic acidosis (pH 7.0) and with an insulin encapsulation rate of 74.50% was identified by investigating the influence factors of pH response value. The morphology of particles was confirmed by different analytical methods, indicating that insulin-loaded mesoporous silica particles maintained the rod-like and orderly hexagonal phase mesoporous structure. The coordination mechanism results showed that half of the amino groups on the carrier were coordinated with Cu, and insulin was successfully coordinated with Cu without any damage on the secondary structure. The amount of insulin coordination with Cu was positively correlated with the pH of the reaction solution. The cytotoxicity result shows that SBA-NH-Cu-Ins was biocompatible with cells in the concentration ranging from 25 to 100 μg·mL. In vivo study preformed on rats showed that the insulin-loaded particles elicited a period hypoglycemic response. Furthermore, fluorescence and UV methods revealed that insulin-loaded mesoporous silica particles had no significant effect on the secondary structure of serum albumin.
在这项工作中，我们研究了将与氨基接枝的介孔硅作为胰岛素的 pH 敏感释放载体的可行性。首先将介孔硅颗粒接枝上氨基。在金属离子配位到介孔孔表面之后，通过与金属离子的配位键将胰岛素负载到介孔硅颗粒上。通过研究 pH 响应值的影响因素，确定了具有在生理环境 pH 值 (7.4) 和糖尿病酸中毒 pH 值 (7.0) 之间的酸敏感性的胰岛素负载介孔硅颗粒，并且胰岛素包封率为 74.50%。通过不同的分析方法证实了颗粒的形态，表明胰岛素负载介孔硅颗粒保持棒状和有序的六方相介孔结构。配位机制结果表明，载体上的一半氨基与 Cu 配位，并且胰岛素成功地与 Cu 配位，而对二级结构没有任何损伤。胰岛素与 Cu 的配位量与反应溶液的 pH 值呈正相关。细胞毒性结果表明 SBA-NH-Cu-Ins 在 25 至 100μg·mL 的浓度范围内与细胞具有生物相容性。在大鼠体内研究表明，负载胰岛素的颗粒引起了一段时间的低血糖反应。此外，荧光和 UV 方法表明，负载胰岛素的介孔硅颗粒对血清白蛋白的二级结构没有显著影响。
