Redox injectable gel protects osteoblastic function against oxidative stress and suppresses alveolar bone loss in a rat peri-implantitis model.

Dental implant surgery is a routine treatment in clinical dentistry. However, implant surgery is associated with an increased risk of bacterially induced peri-implantitis and the production of reactive oxygen species (ROS), with no established treatment. We recently designed a new redox injectable gel (RIG) containing nitroxide radicals for the treatment of peri-implantitis. Here, we investigated the antioxidative effect of RIG as a preventive therapy for ROS-associated peri-implantitis in a rat model of alveolar bone resorption and in vitro. In each rat, the maxillary first molar tooth was replaced with a screw-type implant, and rats were assigned to one of four groups: an implant alone, an implant with infection, implant with infection and treatment with nRIG (a non-nitroxide radical-containing injectable hydrogel) or RIG. We confirmed the long-term retention of RIG in the peri-implant region and found that RIG significantly protected the alveolar bone volume and decreased lipid peroxidation. In culture, we found that RIG restored osteoblast proliferation and differentiation in the presence of hydrogen peroxide (H2O2)-induced oxidative stress. Moreover, using a malondialdehyde assay of lipid peroxidation, we found that RIG suppressed oxidative stress in H2O2-treated rat osteoblasts. Overall, RIG is anticipated as a prophylactic treatment for peri-implantitis and may help preserve oral function. Statement of Significance 1. Implant surgery is associated with an increased risk of bacterially induced peri-implantitis and the production of reactive oxygen species (ROS). We designed a novel redox injectable gel (RIG) containing nitroxide radicals for the treatment of peri-implantitis. In this study, we investigated the antioxidative effect of RIG as a preventive therapy for ROS-associated peri-implantitis in a rat model and in vitro. 2. We showed that treatment with RIG reduces oxidative damage in a rat peri-implantitis model, protecting against bone resorption and a loss of bone density. We showed that RIG inhibits H2O2-mediated decreases in proliferation, osteoblast differentiation, and mineralization, and also against lipid peroxidation in vitro. Our results indicate that RIG has an antioxidative effect of peri-implantitis.

Redox-active injectable gel using polyion complex to achieve sustained release of exenatide and enhance therapeutic efficacy for the treatment of type 2 diabetes.

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.

Chronic treatment with a smart antioxidative nanoparticle for inhibition of amyloid plaque propagation in Tg2576 mouse model of Alzheimer's disease.

The present study aimed to assess whether our newly developed redox nanoparticle (RNPN) that has antioxidant potential decreases Aß levels or prevents Aß 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 Aß(1-40), Aß(1-42) and gamma (γ)-secretase levels, and reduced Aß 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 Aß aggregation, thereby suppressing its adverse side effect.