Syntheses of click PEG-dexamethasone conjugates for the treatment of rheumatoid arthritis

Xin Ming Liu, Ling Dong Quan, Jun Tian, Frederic C. Laquer, Pawel Ciborowski, Dong Wang

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

A novel linear multifunctional polyethylene glycol (PEG)-dexamethasone (Dex) conjugate (click PEG-Dex) was synthesized using facile Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition (a click reaction). Dex was conjugated to the click PEG via an acid-labile hydrazone bond to allow the drug release in a pathophysiological environment. To evaluate click PEGs potential as a versatile drug delivery platform, the click PEG-Dex conjugates were tested in an adjuvant-induced arthritis (AA) rat model. In vivo optical imaging data confirmed the arthrotropism of the conjugates in the arthritic rats. A long-term treatment study revealed that a single click PEG-Dex conjugate administration provided sustained (>15 days) amelioration of ankle joint inflammation to the AA rats. Treatment with an equivalent dose of dexamethasone phosphate sodium (free Dex) only provided temporal resolution of the arthritis, which recurred upon treatment withdrawal. Further histological and bone mineral density comparison between the ankle joints from both click PEG-Dex and free Dex treatment groups confirmed the superior anti-inflammatory and disease modifying effects of the novel polymer-drug conjugates.

Original languageEnglish (US)
Pages (from-to)2621-2628
Number of pages8
JournalBiomacromolecules
Volume11
Issue number10
DOIs
StatePublished - Oct 11 2010

ASJC Scopus subject areas

  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

Fingerprint Dive into the research topics of 'Syntheses of click PEG-dexamethasone conjugates for the treatment of rheumatoid arthritis'. Together they form a unique fingerprint.

  • Cite this