Insulin drug delivery in neurodegeneration

It has been shown that the cascade of biological reactions downstream of insulin administration is involved in brain cognitive functions and their dysfunction in brain degeneration. Therefore, insulin administration could be a potential therapeutic agent for neurodegenerative diseases such as Alzheimer's disease (AD). In order to overcome the biological barriers that prevent the spread of drugs in the brain, nanovectors (e.g. nanogels) can be a valuable aid. Nanogels (NGs) can be produced with high yields by irradiation with a pulsed electron beam of diluted aqueous solutions of water-soluble biocompatible polymers, thus guaranteeing a high degree of sterility. The nanogels used in our experiments were obtained from diluted polyvinyl pyrrolidone (PVP) aqueous solutions functionalized with carboxyl groups and demonstrated high biocompatibility when added to in vitro cell model systems. In vivo, the intraperitoneal injection of NGs conjugated with Insulin (NG-In) and with fluorescent labels allowed to determine the biodistribution in murine systems, in the whole organism and their clearance through the kidneys and the bladder. Furthermore, we observed that the mice injected with NGs did not report stress, discomfort or mortality during the observation time. It can therefore be concluded that, in our experimental conditions, the nanogels did not cause any toxic effect.
Preliminary data indicate that, intranasally administered in mouse, the NG-Insulin (NG-In) complex is able to reach different areas of the brain to a greater extent than free insulin. Furthermore, histopathological analysis of the nasal cavity does not show significant changes in the lining of the epithelial cells indicating that the nano-solution is well tolerated. Although very encouraging results have been obtained, studies are still underway to develop a second generation of nanogels made starting from different polymers. The present research line is the result of a close interdisciplinary collaboration with the Institute of Biomedicine and Molecular Immunology (IBIM, Dr. Marta Di Carlo) of the CNR and with the Department of Industrial and Digital Innovation (DIID, Prof. Clelia Dispenza) of the University of Palermo.

Members:
Daniela Giacomazza (Principal investigator)
Pier Luigi San Biagio