Exploring mesoporous silica nanoparticles as oral insulin carriers: In-silico and in vivo evaluation

Ehsan Salarkia; Mahdis Mehdipoor; Elahe Molaakbari; Ahmad Khosravi; Mohammad Reza Sazegar; Zohreh Salari; Iman Rad; Shahriar Dabiri; Siyavash Joukar; Iraj Sharifi; Guogang Ren

doi:10.1016/j.heliyon.2023.e20430

Exploring mesoporous silica nanoparticles as oral insulin carriers: In-silico and in vivo evaluation

Heliyon. 2023 Sep 26;9(10):e20430. doi: 10.1016/j.heliyon.2023.e20430. eCollection 2023 Oct.

Authors

Affiliations

¹ Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran.
² Faculty of Chemistry, North Tehran Branch, Islamic Azad University, Hakimiyeh, Tehran, Iran.
³ Department of Chemistry, Shahid Bahonar University of Kerman, Kerman, Iran.
⁴ Department of Obstetrics and Gynecology, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
⁵ Afzalipour School of Medicine & Pathology and Stem Cells Research Center, Kerman University of Medical Sciences, Kerman, Iran.
⁶ Neuroscience Research Center, Institute of Basic and Clinical Physiology Sciences, Department of Physiology and Pharmacology, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
⁷ School of Engineering and Computer Science, University of Hertfordshire, Hatfield, AL10 9AB, UK.

Abstract

The advancements in nanoscience have brought attention to the potential of utilizing nanoparticles as carriers for oral insulin administration. This study aims to investigate the effectiveness of synthesized polymeric mesoporous silica nanoparticles (MSN) as carriers for oral insulin and their interactions with insulin and IR through in-silico docking. Diabetic rats were treated with various MSN samples, including pure MSN, Amin-grafted MSN/PEG/Insulin (AMPI), Al-grafted MSN/PEG/Insulin (AlMPI), Zinc-grafted MSN/PEG/Insulin (ZNPI), and Co-grafted MSN/PEG/Insulin (CMPI). The nanocomposites were synthesized using a hybrid organic-inorganic method involving MSNs, graphene oxide, and insulin. Characterization of the nanocomposites was conducted using X-ray diffraction (XRD), Fourier-transform infrared (FTIR) spectroscopy, and scanning electron microscopy (SEM). In vivo tests included the examination of blood glucose levels and histopathological parameters of the liver and pancreas in type 1 diabetic rats. The MSN family demonstrated a significant reduction in blood glucose levels compared to the diabetic control group (p < 0.001). The synthesized nanocomposites exhibited safety, non-toxicity, fast operation, self-repairing pancreas, cost-effectiveness, and high efficiency in the oral insulin delivery system. In the in-silico study, Zn-grafted MSN, Co-grafted MSN, and Al-grafted MSN were selected. Docking results revealed strong interactions between MSN compounds and insulin and IR, characterized by the formation of hydrogen bonds and high binding energy. Notably, Co-grafted MSN showed the highest docking scores of -308.171 kcal/mol and -337.608 kcal/mol to insulin and IR, respectively. These findings demonstrate the potential of polymeric MSN as effective carriers for oral insulin, offering promising prospects for diabetes treatment.

Keywords: Diabetic rat; In-silico; Mesoporous silica nanoparticles; Oral insulin; PEG.