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

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.