Oral nanotherapeutics: effect of redox nanoparticle on microflora in mice with dextran sodium sulfate-induced colitis

Patients with ulcerative colitis (UC) exhibit overproduction of reactive oxygen species (ROS) and imbalance of colonic microflora. We previously developed a novel redox nanoparticle (RNPO), which effectively scavenged ROS in the inflamed mucosa of mice with dextran sodium sulfate (DSS)-induced colitis after oral administration. The objective of this study was to examine whether the orally administered RNPO changed the colonic microflora in healthy mice and those with colitis. RNPO was synthesized by self-assembly of an amphiphilic block copolymer that contains stable nitroxide radicals in hydrophobic side chain via ether linkage. Colitis was induced in mice by supplementing DSS in drinking water for 7 days, and RNPO was orally administered daily during DSS treatment. The alterations of fecal microflora during treatment of DSS and RNPO were investigated using microbiological assays. We investigated that RNPO did not result in significant changes to the fecal microflora in healthy mice. Although total aerobic and anaerobic bacteria were not significantly different between experimental groups, a remarkable increase in commensal bacteria (Escherichia coli and Staphylococcus sp.) was observed in mice with DSS-induced colitis. Interestingly, orally administered RNPO remarkably reduced the rate of increase of these commensal bacteria in mice with colitis. On the basis of the obtained results, it was confirmed that the oral administration of RNPO did not change any composition of bacteria in feces, which strongly suggests a protective effect of RNPO on healthy environments in intestinal microflora. RNPO may become an effective and safe medication for treatment of UC.