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RESEARCH PRODUCT

Biodistribution of Insulin-Nanogels in Mouse: A Preliminary Study for the Treatment of Alzheimer's Disease

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A growing body of evidence shows that Insulin, Insulin Receptor (IR) and IR signaling are involved in brain cognitive functions and their dysfunction is implicated in Alzheimer's disease (AD) neurodegeneration. 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) to deliver the protein into the brain, as a tool for the development of a new therapy against AD. In our preclinical study 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, nanogels 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 by fluorescence analysis and Western blot. Data have shown that insulin signaling is improved in the different brain areas when the protein is conjugated with nanogels with respect to the free insulin. In addition, the histopathological analysis of the nasal cavity shows no significant change in epithelial cell lining indicating that the nano-solution is well tolerated in mouse. These results indicate that the synthesized NG-In was a suitable carrier for insulin delivery in the brain having a higher efficiency than free-insulin.