Safari Mostafa, Kamari Younes, Ghiaci Mehran, Sadeghi-Aliabadi Hojjat, Mirian Mina
a Department of Chemistry , Isfahan University of Technology , Isfahan , Iran.
b Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences , Isfahan University of Medical Sciences , Isfahan , Iran.
Drug Dev Ind Pharm. 2017 May;43(5):862-870. doi: 10.1080/03639045.2016.1220573. Epub 2016 Aug 22.
In this work, a series of composites of insulin (Ins)/zirconium phosphate (ZrP) were synthesized by intercalation method, then, these composites were coated with TiO by sol-gel method to prepare Ins/ZrP@TiO hybrid composites and the drug release of the composites was investigated by using UV-Vis spectroscopy. Ins/ZrP (10, 30, 60 wt%) composites were prepared by intercalation of insulin into the ZrP layers in water. Then Ins/ZrP composites were coated with different amounts of TiO (30, 50, 100 wt %) by using titanium tetra n-butoxide, as precursor. Formation of intercalated Ins/ZrP and Ins/ZrP@TiO hybrid composites was characterized by FT-IR, FE-SEM, BET and XRD analysis. Zeta potential of the optimized Ins/ZrP@TiO hybrid composite was determined -27.2 mV. Cytotoxic effects of the optimized Ins/ZrP@TiO hybrid composite against HeLa and Hek293T cell lines were evaluated using MTT assay and the results showed that designed drug delivery system was not toxic in biological environment. Compared to the Ins/ZrP composites, incorporation of TiO coating enhanced the drug entrapment considerably, and reduced the drug release. The Ins/ZrP composites without TiO coating released the whole drug after 30 min in pH 7.4 (phosphate buffer solution) while the TiO-coated composites released the entrapped drug after 20 h. In addition to increasing the shelf life of hormone, this nanoencapsulation and nanocoating method can convert the insulin utilization from injection to oral and present a painless and more comfortable treatment for diabetics.
在本研究中，通过插层法合成了一系列胰岛素（Ins）/磷酸锆（ZrP）复合材料，然后采用溶胶 - 凝胶法用TiO对这些复合材料进行包覆，制备了Ins/ZrP@TiO杂化复合材料，并利用紫外 - 可见光谱对复合材料的药物释放进行了研究。通过将胰岛素插入水中的ZrP层中制备了Ins/ZrP（10、30、60 wt%）复合材料。然后以前体四丁氧基钛为原料，用不同量的TiO（30、50、100 wt%）对Ins/ZrP复合材料进行包覆。通过傅里叶变换红外光谱（FT - IR）、场发射扫描电子显微镜（FE - SEM）、比表面积分析仪（BET）和X射线衍射（XRD）分析对插层Ins/ZrP和Ins/ZrP@TiO杂化复合材料的形成进行了表征。优化后的Ins/ZrP@TiO杂化复合材料的zeta电位测定为 - 27.2 mV。采用MTT法评估了优化后的Ins/ZrP@TiO杂化复合材料对HeLa和Hek293T细胞系的细胞毒性作用，结果表明所设计的药物递送系统在生物环境中无毒。与Ins/ZrP复合材料相比，TiO涂层的加入显著提高了药物包封率，并降低了药物释放。未涂覆TiO的Ins/ZrP复合材料在pH 7.4（磷酸盐缓冲溶液）中30分钟后释放了全部药物，而涂覆TiO的复合材料在20小时后释放了包封的药物。除了延长激素的保质期外，这种纳米包封和纳米涂层方法可以将胰岛素的使用方式从注射转变为口服，为糖尿病患者提供无痛且更舒适的治疗。
