An oral nanoformulation of insulin : development and characterization of human insulin loaded graphene oxide-sodium alginate-gold nanocomposite in an animal model

Oral administration of insulin can be the most favorable route of administration for the diabetic patients. However, insulin as a biopharmaceutical is susceptible to the harsh conditions in the gastrointestinal tract leading to the destruction of its chemical structure and bioactivity. In the current study, the insulin-loaded gold-graphene oxide-sodium alginate (AuGOSA) nanocomposite was developed and functionalized following several steps. Then, the insulin was loaded on the nanocomposite carrier. The developed nanocarrier was characterized by different methods, including UV/Visible spectroscopy, Fourier-transformed infrared (FT-IR), and scanning electron microscopy (SEM). The amounts of insulin after loading, release and stability were studied by UV/Visible spectroscopy and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). A wide range of pH and a synthetic gastric fluid was adopted to evaluate the protective potential of nanocomposite from insulin degradation. Finally, the biological effect of the prepared formulation on blood glucose levels was assessed in an animal model. The Uv/Visible spectra, FT-IR spectra, and SEM images confirmed the successful synthesis of AuGOSA nanocomposite with a size of 21.76 ± 1.63 nm. The insulin loading was obtained at 71% ± 2. The nanocomposite could prevent insulin degradation in synthetic gastric fluids. At the acidic pH values of 1, 2, and 5, the total insulin release was 13.0%, 13.6%, and 26.5% even after 1 h; however, at alkaline pH values (8 and 9), more than 80% of release was occurred during the first 10 min and reached to 100% after 1 h. Additionally, a gradual and controlled release of insulin was observed for the prepared formulation, which could probably reduce blood glucose fluctuations and drug side effects. The bioactivity of insulin examined in-vivo showed a significant decrease in the blood glucose level compared to the control group. Therefore, the developed insulin-loaded nanocarrier can be considered a promising oral insulin formulation for further studies.