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

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

Research output: Contribution to journalArticle

59 Citations (Scopus)

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

Fingerprint

Dexamethasone
Polyethylene glycols
Rats
dexamethasone 21-phosphate
Cycloaddition
Hydrazones
Drug delivery
Pharmaceutical Preparations
Bone
Phosphates
Minerals
Sodium
Polymers
Anti-Inflammatory Agents
Imaging techniques
Acids

ASJC Scopus subject areas

  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

Cite this

Syntheses of click PEG-dexamethasone conjugates for the treatment of rheumatoid arthritis. / Liu, Xin Ming; Quan, Ling Dong; Tian, Jun; Laquer, Frederic C.; Ciborowski, Pawel S; Wang, Dong.

In: Biomacromolecules, Vol. 11, No. 10, 11.10.2010, p. 2621-2628.

Research output: Contribution to journalArticle

Liu, Xin Ming ; Quan, Ling Dong ; Tian, Jun ; Laquer, Frederic C. ; Ciborowski, Pawel S ; Wang, Dong. / Syntheses of click PEG-dexamethasone conjugates for the treatment of rheumatoid arthritis. In: Biomacromolecules. 2010 ; Vol. 11, No. 10. pp. 2621-2628.
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