Macromolecular glucocorticoid prodrug improves the treatment of dextran sulfate sodium-induced mice ulcerative colitis

Ke Ren, Hongjiang Yuan, Yijia Zhang, Xin Wei, Dong Wang

Research output: Contribution to journalArticle

21 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)71-81
Number of pages11
JournalClinical Immunology
Volume160
Issue number1
DOIs
StatePublished - Sep 1 2015

Keywords

  • Dextran sulfate sodium
  • ELVIS
  • Glucocorticoid
  • HPMA copolymer
  • Inflammatory bowel diseases
  • Prodrug

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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