title: Preparation and antioxidant activity of PEGylated chitosans with different particle sizes.
abstract: The preparation of water-soluble chitosans such as polyethylene glycol (PEG)-grafted derivatives is essential for improving the biocompatibility and water solubility of these types of polysaccharides. In this study, chitosans (CS1; 22 kDa, CS2; 38 kDa, CS3; 52 kDa) with different molecular weights were modified with a succinyl ester derivative of monomethoxypolyethylene glycol (mPEG-COONSu; 2 kDa), and the properties of the resulting conjugates (mPEG-CS1, mPEG-CS2, mPEG-CS3) were investigated. The antioxidant properties of these mPEG-CSs were examined using (1) N-centered radicals derived from 1,1'-diphenyl-2-picrylhydrazyl (DPPH), (2) reducing power, based on their ability to reduce Cu2+ and (3) hydroxyl radicals via the use of ESR spectrometry. The order of their effectiveness was mPEG-CS1>mPEG-CS2>mPEG-CS3, i.e. mPEG-CS1 with a low particle size had the highest scavenging activity of the mPEG-CSs tested. In an in vivo study, we examined the effect of mPEG-CS1 on liver injury, caused by injecting mice with Concanavalin A (Con A). The livers of mice that were treated with mPEG-CS1 were protected from Con A-induced injury. Further, pre-treatment with mPEG-CS1 dramatically reduced the mortality associated with Con A-induced mortality. These findings suggest that mPEG-CS1 could be potentially useful in the treatment of immune-mediated liver injury.
authors: Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Kumamoto 860-0082, Japan. Electronic address: anraku@ph.sojo-u.ac.jp.
authors: Makoto
authors: M
authors: Anraku
authors: Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Kumamoto 860-0082, Japan.
authors: Ayumu
authors: A
authors: Hiraga
authors: Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Kumamoto 860-0082, Japan.
authors: Daisuke
authors: D
authors: Iohara
authors: DDS Research Institute, Sojo University, 4-22-1 Ikeda, Kumamoto 860-0082, Japan.
authors: Kaneto
authors: K
authors: Uekama
authors: Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Sanzo 1, Gakuen-cho, Fukuyama 729-0292, Japan.
authors: Hisao
authors: H
authors: Tomida
authors: Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Kumamoto 860-0082, Japan; DDS Research Institute, Sojo University, 4-22-1 Ikeda, Kumamoto 860-0082, Japan.
authors: Masaki
authors: M
authors: Otagiri
authors: Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Kumamoto 860-0082, Japan; DDS Research Institute, Sojo University, 4-22-1 Ikeda, Kumamoto 860-0082, Japan. Electronic address: fhira@ph.sojo-u.ac.jp.
authors: Fumitoshi
authors: F
authors: Hirayama
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D048271:Chitosan / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000037:antagonists & inhibitors; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D015394:Molecular Structure; D008970:Molecular Weight; D019906:Nuclear Magnetic Resonance, Biomolecular; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D012995:Solubility
chemical_list: D000975:Antioxidants; D016166:Free Radical Scavengers; D017665:Hydroxyl Radical; D011092:Polyethylene Glycols; D048271:Chitosan
keywords: Antioxidant; Chitosan; Liver injury therapy; Polyethylene glycol; Reactive oxygen species