Jermy B Rabindran, Salahuddin Mohammed, Tanimu Gazali, Dafalla Hatim, Almofty Sarah, Ravinayagam Vijaya
Department of NanoMedicine Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia.
Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia.
Pharmaceutics. 2023 Feb 9;15(2):593. doi: 10.3390/pharmaceutics15020593.
An iron-based SBA-16 mesoporous silica (ferrisilicate) with a large surface area and three-dimensional (3D) pores is explored as a potential insulin delivery vehicle with improved encapsulation and loading efficiency. Fe was incorporated into a framework of ferrisilicate using the isomorphous substitution technique for direct synthesis. Fe species were identified using diffuse reflectance spectroscopy. The large surface area (804 m/g), cubic pores (3.2 nm) and insulin loading were characterized using XRD, BET surface area, FTIR and TEM analyses. For pH sensitivity, the ferrisilicate was wrapped with polyethylene glycol (MW = 400 Daltons) (PEG). For comparison, Fe (10 wt%) was impregnated on a Korea Advanced Institute of Science and Technology Number 6 (KIT-6) sieve and Mesocellular Silica Foam (MSU-F). Insulin loading was optimized, and its release mechanism was studied using the dialysis membrane technique (MWCO = 14,000 Da) at physiological pH = 7.4, 6.8 and 1.2. The kinetics of the drug's release was studied using different structured/insulin nanoformulations, including Santa Barbara Amorphous materials (SBA-15, SBA-16), MSU-F, ultra-large-pore FDU-12 (ULPFDU-12) and ferrisilicates. A different insulin adsorption times (0.08-1 h), insulin/ferrisilicate ratios (0.125-1.0) and drug release rates at different pH were examined using the Korsmeyer-Peppas model. The rate of drug release and the diffusion mechanisms were obtained based on the release constant (k) and release exponent (n). The cytotoxicity of the nanoformulation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using human foreskin fibroblast (HFF-1) cells. A low cytotoxicity was observed for this nanoformulation starting at the highest concentrations used, namely, 400 and 800 μg. The hypoglycemic activity of insulin/ferrisilicate/PEG on acute administration in Wistar rats was studied using doses of 2, 5 and 10 mg/kg body weight. The developed facile ferrisilicate/PEG nanoformulation showed a high insulin encapsulation and loading capacity with pH-sensitive insulin release for potential delivery through the oral route.
一种具有大表面积和三维（3D）孔道的铁基SBA - 16介孔二氧化硅（铁硅酸盐）被探索作为一种潜在的胰岛素递送载体，具有提高的包封率和负载效率。使用同晶取代技术将铁掺入铁硅酸盐骨架中以进行直接合成。使用漫反射光谱法鉴定铁物种。使用XRD、BET表面积、FTIR和TEM分析对大表面积（804 m²/g）、立方孔（3.2 nm）和胰岛素负载进行了表征。为了实现pH敏感性，用聚乙二醇（分子量 = 400道尔顿）（PEG）包裹铁硅酸盐。作为比较，将10 wt%的铁浸渍在韩国科学技术院6号（KIT - 6）筛和介孔二氧化硅泡沫（MSU - F）上。优化了胰岛素负载，并在生理pH值7.4、6.8和1.2下使用透析膜技术（截留分子量 = 14,000 Da）研究了其释放机制。使用不同结构/胰岛素纳米制剂，包括圣巴巴拉无定形材料（SBA - 15、SBA - 16）、MSU - F、超大孔FDU - 12（ULPFDU - 12）和铁硅酸盐，研究了药物释放动力学。使用Korsmeyer - Peppas模型研究了不同的胰岛素吸附时间（0.08 - 1小时）、胰岛素/铁硅酸盐比例（0.125 - 1.0）以及在不同pH下的药物释放速率。基于释放常数（k）和释放指数（n）获得了药物释放速率和扩散机制。使用人包皮成纤维细胞（HFF - 1）通过3 -（4,5 - 二甲基噻唑 - 2 - 基）- 2,5 - 二苯基四氮唑溴盐（MTT）试验评估了纳米制剂的细胞毒性。在使用的最高浓度即400和800 μg时观察到该纳米制剂具有低细胞毒性。使用2、5和10 mg/kg体重的剂量研究了胰岛素/铁硅酸盐/PEG对Wistar大鼠急性给药后的降血糖活性。所开发的简便的铁硅酸盐/PEG纳米制剂显示出高胰岛素包封率和负载能力，以及对pH敏感的胰岛素释放，有望通过口服途径递送。
