title: Suppression of NSAID-induced small intestinal inflammation by orally administered redox nanoparticles.
abstract: Patients regularly taking non-steroidal anti-inflammatory drugs (NSAIDs) such as indomethacin (IND) have a risk of small intestinal injuries. In this study, we have developed an oral nanotherapeutics by using a redox nanoparticle (RNP(O)), which is prepared by self-assembly of an amphiphilic block copolymer that possesses nitroxide radicals as side chains of hydrophobic segment via ether linkage, to reduce inflammation in mice with IND-induced small intestinal injury. The localization and accumulation of RNP(O) in the small intestine were determined using fluorescent-labeled RNP(O) and electron spin resonance. After oral administration, the accumulation of RNP(O) in both the jejunum and ileum tissues was about 40 times higher than those of low-molecular-weight nitroxide radical compounds, and RNP(O) was not absorbed into the bloodstream via the mesentery, thereby avoiding the adverse effects of nitroxide radicals in the entire body. RNP(O) remarkably suppressed inflammatory mediators such as myeloperoxidase, superoxide anion, and malondialdehyde in the small intestines of IND-treated mice. Compared to low-molecular-weight nitroxide radical compounds, RNP(O) also significantly increased the survival rate of mice treated daily with IND. On the basis of these results, RNP(O) is promising as a nanotherapeutics for treatment of inflammation in the small intestine of patients receiving NSAIDs.
authors.affiliation: Department of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8573, Japan.
authors.forename: Sha
authors.initials: S
authors.lastname: Sha
authors.forename: Long Binh
authors.initials: LB
authors.lastname: Vong
authors.forename: Pennapa
authors.initials: P
authors.lastname: Chonpathompikunlert
authors.forename: Toru
authors.initials: T
authors.lastname: Yoshitomi
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Matsui
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nagasaki
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D007249:Inflammation / Q000139:chemically induced* / Q000188:drug therapy*; D007421:Intestine, Small / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D051379:Mice; D053758:Nanoparticles; D010084:Oxidation-Reduction
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal
keywords: Antioxidant; Inflammation; Intestinal mucosa; NSAIDs; Nanomedicine; Reactive oxygen species