Bioreabsorbable polymeric nanodevice as peptide controlled delivery system to Alzheimer's disease therapy

Abstract

Alzheimer's Disease (AD) is a neurodegenerative pathology that affects 36 million people worldwide. Type 2 Diabetes Mellitus (T2DM) is a risk factor for AD, as this dementia has been linked to impaired insulin signalling in the brain, consequently, drugs that enhance this signalling may have therapeutic potential for AD. Several studies have shown that GLP-1 (glucagon-like peptide-1) and GIP (gastric inhibitory peptide), endogenous incretin hormones that enhances insulin secretion and reduces blood glucose levels, have many neuroprotective properties and are attractive alternatives to treat AD. Interestingly, a novel unimolecular dual incretin (GLP-1/GIP) peptide was developed to treat T2DM patients. In parallel, a technological innovation has been developed, testing biodegradable polymeric nanofibers as drug carriers for controlled release system due to their high functional features and controlled release in the body. For this reason, this study intends to associate the use of polymeric nanofibers and the novel dual incretin peptide in order to treat AD, in other words, we aim to develop a nanodevice able to provide slow and controlled release of this peptide in the organism, evaluating the effects of it in AD. The peptide will be incorporated into the nanofibers and a concentration-time curve will be performed in order to investigate peptide release and if it is long lasting in the organism. We intend to evaluate the therapy effects in intracellular organelles in vitro, using the cell line SH-SY5Y, human neuroblastoma, oxidatively stressed, in order to provide further evidence of neuronal metabolism after treatment. The behaviour will also be evaluated in vivo, in APP/PS1 transgenic mice, an animal model for AD. The nanodevice containing the peptide will be intraperitoneally incorporated in mice organism. Memory tasks and, subsequently, immunohistochemical analysis will be performed. It is expected to observe that this nanodispositive developed will provide long lasting release of the peptide, reducing inflammatory processes and achiving neuroprotective properties. (AU)