Suppression of NSAID-induced small intestinal inflammation by orally administered redox nanoparticles

• Published in: Biomaterials 2013-11, Vol.34 (33), p.8393-8400
• Main Authors: Sha, Sha, Vong, Long Binh, Chonpathompikunlert, Pennapa, Yoshitomi, Toru, Matsui, Hirofumi, Nagasaki, Yukio
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Animals; Anti-Inflammatory Agents, Non-Steroidal - toxicity; Antioxidant; Dentistry; Inflammation; Inflammation - chemically induced; Inflammation - drug therapy; Intestinal mucosa; Intestine, Small - drug effects; Intestine, Small - pathology; Male; Mice; Nanomedicine; Nanoparticles; NSAIDs; Oxidation-Reduction; Reactive oxygen species
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2013.06.032

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 (RNPO ), 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 RNPO in the small intestine were determined using fluorescent-labeled RNPO and electron spin resonance. After oral administration, the accumulation of RNPO in both the jejunum and ileum tissues was about 40 times higher than those of low-molecular-weight nitroxide radical compounds, and RNPO was not absorbed into the bloodstream via the mesentery, thereby avoiding the adverse effects of nitroxide radicals in the entire body. RNPO 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, RNPO also significantly increased the survival rate of mice treated daily with IND. On the basis of these results, RNPO is promising as a nanotherapeutics for treatment of inflammation in the small intestine of patients receiving NSAIDs.