Design of high-performance anti-adhesion agent using injectable gel with an anti-oxidative stress function.
Postsurgical tissue adhesion formation caused by inflammation and oxidative stress is one of the serious issues because it induces severe clinical disorders. In this study, we designed redox injectable gel (RIG) which covalently possesses nitroxide radicals as a reactive oxygen species (ROS) scavenger for high performance anti-adhesion agent. The redox flower micelles exhibiting gelation under physiological conditions were prepared by a polyion complex (PIC) between polyamine-PEG-polyamine triblock copolymer possessing nitroxide radicals as a side chain of polyamine segments and poly(acrylic acid). RIG showed prolonged local retention in the abdominal cavity of the mice, which was monitored by in vivo imaging system (IVIS). Compared with a commercial anti-adhesion agent (Seprafilm(®), Genzyme, Cambridge, MA), RIG dramatically inhibited the formation of tissue adhesions via a combination of physical separation and biological elimination of generated ROS in talc-induced adhesion model mice. Treatment with RIG suppressed inflammatory cytokines and neutrophil invasion, suppressing the increase in peritoneal membrane thickness. It is also emphasized that RIG suppressed the increase of white blood cells level, indicating that the present RIG treatment effectively prevents diffusion of local inflammation to entire body. These findings indicate that RIG has a great potential as a high performance anti-adhesion agent.
Department of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennoudai 1-1-1, Ibaraki 305-8573, Japan.
Hiroyuki
H
Nakagawa
Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Tokyo 113-8655, Japan.
Yoko
Y
Matsumoto
Department of Otorhinolaryngology and Head and Neck Surgery, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Tokyo 113-8655, Japan.
Yu
Y
Matsumoto
Laboratory Animal Resource Center, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan; Master's School of Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8573, Japan.
Yoshihiro
Y
Miwa
Department of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennoudai 1-1-1, Ibaraki 305-8573, Japan; Master's School of Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8573, Japan; Satellite Laboratory, International Center for Materials Nanoarchitectonics (WPI-MANA), National Institute for Materials Science (NIMS), University of Tsukuba, Tennoudai 1-1-1, Ibaraki 305-8573, Japan. Electronic address: yukio@nagalabo.jp.
Yukio
Y
Nagasaki
D000180:Acrylic Resins / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D005782:Gels / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D007267:Injections; D008807:Mice, Inbred BALB C; D008823:Micelles; D009589:Nitrogen Oxides / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D011073:Polyamines / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D000267:Tissue Adhesions / Q000517:prevention & control*
D000180:Acrylic Resins; D000975:Antioxidants; D005782:Gels; D008823:Micelles; D009589:Nitrogen Oxides; D011073:Polyamines; D011092:Polyethylene Glycols; C006903:carbopol 940; C039900:nitroxyl
Anti-adhesive agent; Polyion-complex micelle; Reactive oxygen species; Redox injectable gel