结肠炎
化学
溃疡性结肠炎
药理学
一氧化氮介导的自由基聚合
炎症
胃肠道
体内分布
炎症性肠病
生物化学
免疫学
医学
病理
共聚物
有机化学
自由基聚合
疾病
聚合物
体外
作者
Long Binh Vong,Tsutomu Tomita,Toru Yoshitomi,Hirofumi Matsui,Yukio Nagasaki
出处
期刊:Gastroenterology
[Elsevier]
日期:2012-10-01
卷期号:143 (4): 1027-1036.e3
被引量:158
标识
DOI:10.1053/j.gastro.2012.06.043
摘要
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.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).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.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.
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