Affiliations: [a]
Department of Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| [b]
Department of Pharmaceutics, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran
| [c]
Department of Biochemistry, Shahrood Branch, Islamic Azad University, Shahrood, Iran
| [d]
Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| [e] Endometrium and Endometriosis Research Centre, Hamadan University of Medical Sciences, Hamadan, Iran
Correspondence:
[*]
Corresponding author: Roghayeh Abbasalipourkabir, Department of Biochemistry, School of Medicine, Hamadan University of Medical Sciences, 65178 Hamadan, Iran. Tel.: +98 81 3838 0572; Mobile: +98 918 311 6910; Fax: +98 81 38380208; E-mail: rpourkabir@hotmail.com; abbasalipourkabir@umsha.ac.ir; orcid.org/0000-0002-6345-1410.
Abstract: Background:Subcutaneous injection of insulin can lead to problems such as hypoglycemia and edema. Objective: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. Methods: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. Results: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. Conclusions: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.
