title: An orally administered redox nanoparticle that accumulates in the colonic mucosa and reduces colitis in mice.
abstract: OBJECTIVE
  Drugs used to treat patients with ulcerative colitis are not always effective because of nonspecific distribution, metabolism in the gastrointestinal tract, and side effects. We designed a nitroxide radical-containing nanoparticle (RNP(O)) that accumulates specifically in the colon to suppress inflammation and reduce the undesirable side effects of nitroxide radicals.
  
  
  METHODS
  RNP(O) was synthesized by assembly of an amphiphilic block copolymer that contains stable nitroxide radicals in an ether-linked hydrophobic side chain. Biodistribution of RNP(O) in mice was determined from radioisotope and electron spin resonance measurements. The effects of RNP(O) were determined in mice with dextran sodium sulfate (DSS)-induced colitis and compared with those of low-molecular-weight drugs (4-hydroxyl-2,2,6,6-tetramethylpiperidine-1-oxyl [TEMPOL] or mesalamine).
  
  
  RESULTS
  RNP(O), with a diameter of 40 nm and a shell of poly(ethylene glycol), had a significantly greater level of accumulation in the colonic mucosa than low-molecular-weight TEMPOL or polystyrene latex particles. RNP(O) was not absorbed into the bloodstream through the intestinal wall, despite its long-term retention in the colon, which prevented its distribution to other parts of the body. Mice with DSS-induced colitis had significantly lower disease activity index and less inflammation following 7 days of oral administration of RNP(O) compared with mice with DSS-induced colitis or mice given low-molecular-weight TEMPOL or mesalamine.
  
  
  CONCLUSIONS
  We designed an orally administered RNP(O) that accumulates specifically in the colons of mice with colitis and is more effective in reducing inflammation than low-molecular-weight TEMPOL or mesalamine. RNP(O) might be developed for treatment of patients with ulcerative colitis.
authors: Department of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Japan.
authors: Long Binh
authors: LB
authors: Vong
authors: Tsutomu
authors: T
authors: Tomita
authors: Toru
authors: T
authors: Yoshitomi
authors: Hirofumi
authors: H
authors: Matsui
authors: Yukio
authors: Y
authors: Nagasaki
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000975:Antioxidants / Q000493:pharmacokinetics / Q000627:therapeutic use; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D003106:Colon / Q000201:enzymology / Q000378:metabolism*; D003497:Cyclic N-Oxides / Q000493:pharmacokinetics / Q000627:therapeutic use; D016264:Dextran Sulfate; D053583:Interleukin-1beta / Q000378:metabolism; D007413:Intestinal Mucosa / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D019804:Mesalamine / Q000627:therapeutic use; D051379:Mice; D008813:Mice, Inbred ICR; D053758:Nanoparticles / Q000627:therapeutic use*; D009589:Nitrogen Oxides / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D009195:Peroxidase / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors; D012720:Severity of Illness Index; D013113:Spin Labels; D013481:Superoxides / Q000378:metabolism; D015996:Survival Rate
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D003497:Cyclic N-Oxides; D053583:Interleukin-1beta; D009589:Nitrogen Oxides; D017382:Reactive Oxygen Species; D013113:Spin Labels; D013481:Superoxides; D019804:Mesalamine; D016264:Dextran Sulfate; D009195:Peroxidase; C039900:nitroxyl; C001803:tempol