Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China.
J Colloid Interface Sci. 2020 Feb 15;560:690-700. doi: 10.1016/j.jcis.2019.10.118. Epub 2019 Nov 1.
Numerous types of mesoporous silica nanoparticles (MSNs) have been studied as carriers for small molecular drugs. However, few reports have been conducted on small MSNs having large pores, and that are suitable for loading and orally delivering therapeutic proteins. In particular, their protective properties against aggregation and enzymatic hydrolysis of loaded proteins have been rarely studied. In this study, mesocellular silica foams (MCFs) with large and different pore sizes were prepared. The loading and release behaviors of three model proteins with different molecular weights were studied. The protective properties of the MCFs against enzymatic hydrolysis of the loaded proteins were tested by sodium dodecyl sulfate polyacrylamide gel electrophoresis and high-performance liquid chromatography. The protecting effects of the MCFs against conformational change and aggregation of the loaded proteins were evaluated by circular dichroism and synchronous fluorescence spectra. Diabetic mice were inducted to evaluate in a preliminary manner the in vivo hypoglycemic effect of insulin loaded MCFs. The prepared MCFs showed rapid and high drug loading (up to 43%) of proteins. The release of proteins was tunable depending on the pore size. The lysozyme loaded MCFs could release 87% intact protein after incubation with pancreatin for 0.5 h. The digestion times for the insulin loaded in MCFs were prolonged to twice that of naked insulin. The secondary conformational changes for the insulin loaded in MCFs were only 1/40 to 1/20 of that of naked insulin incubated with Zn. Orally administered insulin-loaded MCF could reduce the blood glucose level to 69%. The prepared MCFs could effectively protect the loaded proteins from aggregation and enzymatic hydrolysis, thus exhibiting potential for application as carriers for protein delivery.
大量类型的介孔硅纳米粒子 (MSNs) 已被研究作为小分子药物的载体。然而，对于具有大孔且适合负载和口服递送治疗性蛋白质的小 MSNs，报道甚少。特别是，它们对负载蛋白质的聚集和酶解的保护性能很少被研究。在本研究中，制备了具有大孔和不同孔径的中孔硅泡沫 (MCFs)。研究了三种不同分子量的模型蛋白质的负载和释放行为。通过十二烷基硫酸钠聚丙烯酰胺凝胶电泳和高效液相色谱法测试了 MCFs 对负载蛋白质的酶解的保护性能。通过圆二色性和同步荧光光谱评估了 MCFs 对负载蛋白质构象变化和聚集的保护作用。通过诱导糖尿病小鼠初步评估了负载胰岛素的 MCFs 的体内降血糖作用。所制备的 MCFs 对蛋白质具有快速和高载药率（高达 43%）。蛋白质的释放可以根据孔径大小进行调节。在与胰蛋白酶孵育 0.5 小时后，溶菌酶负载的 MCFs 可以释放 87%完整的蛋白质。负载胰岛素的 MCFs 的消化时间延长到裸胰岛素的两倍。负载胰岛素的 MCFs 的二级构象变化仅为与 Zn 孵育的裸胰岛素的 1/40 到 1/20。口服给予负载胰岛素的 MCF 可将血糖水平降低至 69%。所制备的 MCFs 可以有效地保护负载蛋白质免受聚集和酶解，因此具有作为蛋白质递送载体的应用潜力。
