High energy radiation processing for the synthesis of insulin nanocarriers for the development of a new strategy for the treatment of Alzheimer's Disease

Abstract

Nanogels are nanoscalar polymeric networks, characterized by a dynamic internal structure and a flexible adaptive shape. When they are used as drug carriers, their flexibility and shape changing ability can facilitate the bypass of biological barriers, ensure protection of the payload and enable interaction of any attached ligand with its receptors. Poly(N-vinyl pyrrolidone)-co-acrylic acid nanogels (NGs) have been produced by ebeam irradiation of diluted aqueous solutions of a water-soluble polymer in the presence of a small amount of acrylic acid. In particular, industrial accelerators and the typical set-ups and doses applied for sterilization have been used. [1, 2] Particle size, molecular weight and functionalization can be controlled by a proper selection of polymer concentration and irradiation parameters, such as dose-rate and total dose imparted [3]. In recent years, a growing body of evidence has linked insulin resistance and insulin action to Alzheimer’s Disease (AD), a condition also referred to as Type 3 Diabetes (T3D) [4,5]. Recently, it has been demonstrated that insulin is capable of reducing toxicity induced by A oligomers, the protein mainly involved in AD onset, by inhibition of the intrinsic apoptotic pathway [6]. Moreover, activation of insulin signaling provides a neuroprotective mechanism to counteract oxidative stress, mitochondrial damage and neurodegeneration triggered by A oligomers in neuroblastoma cells [7]. In the present work NGs have been conjugated to insulin (NG-In) to defend the hormone from enzymatic degradation, facilitate its crossing through a blood brain barrier model and protect the LAN5 cells from the damages induced by A oligomers addiction.