title: Macromolecular glucocorticoid prodrug improves the treatment of dextran sulfate sodium-induced mice ulcerative colitis.
abstract: 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.
authors: Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors: Ke
authors: K
authors: Ren
authors: Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors: Hongjiang
authors: H
authors: Yuan
authors: Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors: Yijia
authors: Y
authors: Zhang
authors: Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors: Xin
authors: X
authors: Wei
authors: Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA. Electronic address: dwang@unmc.edu.
authors: Dong
authors: D
authors: Wang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis; D018938:Caco-2 Cells; D002460:Cell Line; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000473:pathology; D003907:Dexamethasone / Q000627:therapeutic use*; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D011355:Prodrugs / Q000627:therapeutic use*; D011897:Random Allocation
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D005938:Glucocorticoids; D011355:Prodrugs; D003907:Dexamethasone; D016264:Dextran Sulfate
keywords: Dextran sulfate sodium; ELVIS; Glucocorticoid; HPMA copolymer; Inflammatory bowel diseases; Prodrug