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

Long Binh Vong, Toru Yoshitomi, Kazuya Morikawa, Shinji Saito, Hirofumi Matsui, Yukio Nagasaki

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. 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. 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. 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.