No abstract

The present study aimed to assess whether our newly developed redox nanoparticle (RNPN) that has antioxidant potential decreases Aβ levels or prevents Aβ aggregation associated with oxidative stress. The transgenic Tg2576 Alzheimer’s disease (AD) mice were used to investigate the effect of chronic ad libitum drinking of RNPN solution for 6 months, including memory and learning functions, antioxidant activity, and amyloid plaque aggregation. The results showed that RNPN-treated mice had significantly attenuated cognitive deficits of both spatial and non-spatial memories, reduced oxidative stress of lipid peroxide, and DNA oxidation. RNPN treatment increased the percent inhibition of superoxide anion and glutathione peroxidase activity, neuronal densities in the cortex and hippocampus, decreased Aβ(1-40), Aβ(1-42) and gamma (γ)-secretase levels, and reduced Aβ plaque observed using immunohistochemistry analysis and thioflavin S staining. Our results suggest that RNPN may be a promising candidate for AD therapy because of its antioxidant properties and reduction in Aβ aggregation, thereby suppressing its adverse side effect.

To provide sustained release of exenatide and enhance therapeutic efficacy for the treatment of type 2 diabetes compared to the existing products for exenatide, we developed an exenatide‐loaded, redox‐active, injectable gel (Exe@RIG). This injectable gel is formed by a polyion complex (PIC) comprising three components, (1) cationic polyamine–poly(ethylene glycol)–polyamine triblock copolymer possessing reactive oxygen species (ROS)‐scavenging moieties as side chains, (2) anionic poly(acrylic acid), and (3) exenatide. The mixture formed exenatide‐loaded PIC flower micelles at room temperature, which immediately converted to a gel under physiological conditions. Owing to electrostatic interactions between exenatide and the PIC gel network, RIG was able to provide sustained release of exenatide without a significant initial burst. Subcutaneous injection of Exe@RIG once a week prevented the increase in glucose concentration significantly in db/db mice compared to those in control groups. In addition, Exe@RIG suppressed the degeneration of pancreatic islets, which is reported to be caused by increased ROS. Our result indicates that Exe@RIG has the potential to provide a long acting exenatide as well as enhanced efficacy in the treatment of type 2 diabetes compared to the existing products. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1107–1113, 2019.