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

Background: Patients with ulcerative colitis (UC) exhibit overproduction of reactive oxygen species (ROS) and imbalance of colonic microflora. We previously developed a novel redox nanoparticle (RNP^O), 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 RNP^O changed the colonic microflora in healthy mice and those with colitis. Methods: RNP ^O 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 RNP^O was orally administered daily during DSS treatment. The alterations of fecal microflora during treatment of DSS and RNP^O were investigated using microbiological assays. Results: We investigated that RNP^O 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 RNP ^O remarkably reduced the rate of increase of these commensal bacteria in mice with colitis. Conclusions: On the basis of the obtained results, it was confirmed that the oral administration of RNP^O did not change any composition of bacteria in feces, which strongly suggests a protective effect of RNP^O on healthy environments in intestinal microflora. RNP ^O may become an effective and safe medication for treatment of UC.