Macromolecular glucocorticoid prodrug improves the treatment of dextran sulfate sodium-induced mice ulcerative colitis
Macromolecular glucocorticoid prodrug improves the treatment of dextran sulfate sodium-induced mice ulcerative colitis
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DOI：
10.1016/j.clim.2015.03.027
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发表时间：
2015-09-01
影响因子：
8.6
通讯作者：
Wang, Dong
中科院分区：
文献类型：
--
作者：
Ren, Ke;Yuan, Hongjiang;Wang, Dong
为改善炎症性肠病（IBD）的治疗，开发了地塞米松（Dex）的大分子前药（P-Dex）。通过给小鼠喂食葡聚糖硫酸钠诱导结肠炎症。每天腹膜内注射游离Dex或单次静脉内注射P-Dex、PBS或游离聚合物处理小鼠。与对照组相比，P-Dex和游离Dex均可降低疾病活动指数和组织学评分。单次注射1/4当量Dex的P-Dex治疗效果优于每日游离Dex治疗。机制研究发现P-Dex可靶向炎症结肠，并被上皮细胞和局部炎性浸润物滞留，提示P-Dex的疗效提高可能与其炎症靶向、亚细胞加工和活化有关。总的来说，这些数据支持我们的假设，即糖皮质激素大分子前药的开发可能有潜力改善IBD的临床治疗。(C)2015 Elsevier Inc. All rights reserved.
A macromolecular prodrug (P-Dex) of dexamethasone (Dex) was developed to improve the treatment of inflammatory bowel disease (IBD). Colonic inflammation was induced by feeding mice with dextran sulfate sodium. Mice were treated with daily i.p. injection of free Dex or single i.v. injection of P-Dex, PBS or free polymer. Both P-Dex and free Dex could lower disease activity index and histology scores when compared to the controls. A single injection of P-Dex with 1/4 equivalent Dex dose had a better therapeutic effect than daily free Dex treatment. Mechanism study found that P-Dex could target the inflamed colon, and be retained by epithelial cells and local inflammatory infiltrates, suggesting that the improved efficacy of P-Dex may be attributed to its inflammation targeting, subcellular processing and activation. Collectively, these data support our hypothesis that the development of macromolecular prodrug of glucocorticoid may have the potential to improve the clinical management of IBD. (C) 2015 Elsevier Inc. All rights reserved.