title: Redox-active injectable gel using thermo-responsive nanoscale polyion complex flower micelle for noninvasive treatment of local inflammation.
abstract: Reactive oxygen species (ROS) scavengers have not been widely used for treatment of local inflammatory reactions such as arthritis and periodontal disease because they are rapidly eliminated from the inflamed site, which results in a low therapeutic effect. Therefore, to enhance the local retention time of ROS scavengers, we developed a redox-active injectable gel (RIG) system by using poly[4-(2,2,6,6-tetramethylpiperidine-N-oxyl)aminomethylstyrene]-b-poly(ethylene glycol)-b-poly[4-(2,2,6,6-tetramethylpiperidine-N-oxyl)aminomethylstyrene] (PMNT-PEG-PMNT) triblock copolymer, which possesses ROS scavenging nitroxide radicals as side chains of the PMNT segment. Cationic PMNT segment in PMNT-PEG-PMNT forms polyion complexes with anionic poly(acrylic acid) (PAAc) to form a flower-like micelle (ca. 79 nm), which exhibits in situ thermo-irreversible gelation under physiological conditions. We confirmed the prolonged site-specific retention time of RIG by performing in vivo noninvasive electron spin resonance imaging and quantitative evaluation. In contrast to low-molecular-weight nitroxide radical compounds that disappeared from injection sites in less than 1h after subcutaneous injection, 40% of the RIG remained even at 3 days. We also found that RIG inhibits neutrophil infiltration and cytokine production, which leads to suppression of hyperalgesia. These findings indicate the potential of RIG as an innovative approach for treatment of local inflammation.
authors.affiliation: Department of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba 305-8573, Japan.
authors.forename: Min Ley
authors.initials: ML
authors.lastname: Pua
authors.forename: Toru
authors.initials: T
authors.lastname: Yoshitomi
authors.forename: Pennapa
authors.initials: P
authors.lastname: Chonpathompikunlert
authors.forename: Aki
authors.initials: A
authors.lastname: Hirayama
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nagasaki
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000627:therapeutic use; D001168:Arthritis / Q000188:drug therapy*; D003692:Delayed-Action Preparations / Q000737:chemistry*; D005782:Gels / Q000737:chemistry; D007249:Inflammation / Q000188:drug therapy; D007267:Injections; D007477:Ions / Q000737:chemistry; D008297:Male; D051379:Mice; D008823:Micelles; D009589:Nitrogen Oxides / Q000008:administration & dosage* / Q000627:therapeutic use; D010084:Oxidation-Reduction; D044367:Phase Transition; D010880:Piperidines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D020058:Styrene / Q000737:chemistry; D013696:Temperature
chemical_list: D000180:Acrylic Resins; D000975:Antioxidants; D003692:Delayed-Action Preparations; D005782:Gels; D007477:Ions; D008823:Micelles; D009589:Nitrogen Oxides; D010880:Piperidines; D011092:Polyethylene Glycols; D020058:Styrene; C551336:2,2,6,6-tetramethylpiperidide; C006903:carbopol 940; C039900:nitroxyl
keywords: 2,2′-Azobisisobutyronitrile (PubChem CID: 6547); 4-Amino-TEMPO (PubChem CID: 550942); Antioxidant; Chloromethylstyrene (PubChem CID: 16211416); Inflammation; Injectable hydrogel; Micelle; Poly(acrylic acid) (PubChem CID: 6581); Poly(ethylene glycol) (PubChem CID: 174); Polyion complex; Sol–gel process; λ-Carrageenan (PubChem CID: 11966249)