Kalantarian Giti, Ziamajidi Nasrin, Mahjub Reza, Goodarzi Mohammad Taghi, Saidijam Massoud, Soleimani Asl Sara, Abbasalipourkabir Roghayeh
Department of Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Department of Pharmaceutics, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran.
Restor Neurol Neurosci. 2018;36(4):571-581. doi: 10.3233/RNN-170807.
Subcutaneous injection of insulin can lead to problems such as hypoglycemia and edema.
The purpose of this research was to evaluate the effect of oral insulin-coated trimethyl chitosan nanoparticles on control of glycemic status, IGF-1 and IGF-2 levels, and apoptosis in the hippocampus of rats with diabetes mellitus.
Insulin-coated trimethyl chitosan nanoparticles were prepared by the polyelectrolyte complex method (PEC) method. Insulin loading content, loading efficiency, quantity and quality of particle size were evaluated. In vivo study was performed in different treatment groups of male Wistar rats with diabetes mellitus by insulin-coated trimethyl chitosan nanoparticles or subcutaneous injection of trade insulin. The duration of diabetes was eight weeks and the treatment was started after that time and continued for another two weeks. Body weight, fasting blood glucose (FBS), hippocampal apoptosis, and immunohistochemical (IHC) protein levels of IGF-1 and IGF-2 were assessed at the end of the experiments.
The size and polydispersity indexes were 533 nanometers and 0.533, respectively. Insulin coated trimethyl chitosan nanoparticles showed high loading efficiency (97.67% ) and loading content (48.83% ). The spherical shape of nanoparticle was confirmed by transmission electron microscopic (TEM). The amine, amide, ether and aliphatic groups were evaluated using FT-IR spectrophotometer which represented the correctness of the insulin coated trimethyl chitosan nanoparticles. Although the apoptotic index was not changed either by insulin-coated nano-particles or commercial insulin, in vivo results showed the efficacy of insulin-coated nanoparticles as well as commercial insulin in compensated weight loss, FBS and protein levels of IGF-1 and IGF-2.
The present study showed the efficacy of insulin coated nanoparticle in oral route manner that can be tested in Phase I- III clinical trials. However, a behavioral study could reveal the efficacy of insulin-loaded nanoparticles in the improvement of cognitive changes through the modulation of IGF-1 and IGF-2 levels in the hippocampus.
皮下注射胰岛素可导致低血糖和水肿等问题。
本研究旨在评估口服胰岛素包被的三甲基壳聚糖纳米粒对糖尿病大鼠血糖状态控制、胰岛素样生长因子-1（IGF-1）和胰岛素样生长因子-2（IGF-2）水平以及海马体细胞凋亡的影响。
采用聚电解质络合法制备胰岛素包被的三甲基壳聚糖纳米粒。评估胰岛素负载量、负载效率、粒径数量和质量。对雄性Wistar糖尿病大鼠不同治疗组进行体内研究，分别给予胰岛素包被的三甲基壳聚糖纳米粒或皮下注射市售胰岛素。糖尿病病程为8周，在此之后开始治疗并持续2周。实验结束时评估体重、空腹血糖（FBS）、海马体细胞凋亡以及IGF-1和IGF-2的免疫组化（IHC）蛋白水平。
粒径和多分散指数分别为533纳米和0.533。胰岛素包被的三甲基壳聚糖纳米粒显示出高负载效率（97.67%）和负载量（48.83%）。通过透射电子显微镜（TEM）确认纳米粒呈球形。使用傅里叶变换红外光谱仪（FT-IR）对胺基、酰胺基、醚基和脂肪族基团进行评估，表明胰岛素包被的三甲基壳聚糖纳米粒制备正确。尽管胰岛素包被纳米粒或市售胰岛素均未改变细胞凋亡指数，但体内研究结果显示胰岛素包被纳米粒以及市售胰岛素在减轻体重、降低FBS以及提高IGF-1和IGF-2蛋白水平方面均有效。
本研究表明胰岛素包被纳米粒经口服途径有效，可在I - III期临床试验中进行测试。然而，行为学研究可能揭示负载胰岛素的纳米粒通过调节海马体中IGF-1和IGF-2水平改善认知变化的效果。
