Insulin-nanogels: preliminary study in mouse for the treatment of Alzheimer's disease

Abstract

A growing body of evidence shows that Insulin, Insulin Receptor (IR) and IR signalling are involved in brain cognitive functions and their dysfunction is implicated in Alzheimer’s disease (AD). Thus, administration of insulin could be a strategy for AD treatment. For this aim we have designed, synthesized and characterized a nanogel system (NG) that has been conjugated to insulin molecules (NG-In) (1) as new therapeutic approach against AD. In our preclinical studies in mice, intraperitoneal injection of fluorescent-labeled NG has allowed to determine the biodistribution of NG vs time in the whole body and its clearance through the kidneys and bladder. Furthermore, we have observed that mice injected with nanogel did not experience stress, discomfort, nor mortalities have been recorded during the observation time. Thus, we may conclude that under our experimental conditions, nonogels did not cause any toxic effects and they are eliminated in urine. The administration of NG-In through the intranasal route to study its brain distribution has been done. Data have shown that different insulin levels were present in brain areas when the protein is conjugated with nanogels with respect to the free insulin. These results indicate that the synthesized NG-In is a suitable carrier for insulin delivery in the brain having a higher efficiency than free-insulin. 1. Picone, P. et al, (2016) Biomaterials 80: 179-94