Novel dexamethasone-HPMA copolymer conjugate and its potential application in treatment of rheumatoid arthritis

Dong Wang, Scott C. Miller, Xin Ming Liu, Brian Anderson, X. Sherry Wang, Steven R. Goldring

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease of unknown etiology. Effective treatment of this disorder has been hampered by the lack of availability of agents that selectively target affected joint tissue. We developed a novel pH-sensitive drug delivery system of dexamethasone (Dex) based on an N-(2-hydroxypropyl)methacrylamide copolymer (P-Dex) and have shown that the delivery system specifically accumulates in inflamed joints in an animal model of arthritis. We hypothesize that the arthrotropism of the delivery system and the local acidosis-mediated drug release provide superior therapeutic efficacy and potentially reduced side effects in RA treatment. The initial in vitro drug-release study confirmed that the Dex release is indeed dependent upon the environmental pH. At pH 5, 37°C, the conjugate shows the highest level of drug release. When administered systemically in an adjuvant-induced arthritis rat model, P-Dex offers superior and longer-lasting anti-inflammatory effects compared with systemically administered free Dex. In addition, greater bone and cartilage preservation was observed with the P-Dex treatment compared with free Dex treatment. Our data indicate that the differential effect of the conjugate is related to its selective accumulation, potential macrophage-mediated retention, and pH-sensitive drug release (extracellular and intracellular) in arthritic joints. This newly developed drug delivery system provides a unique method for selective targeting of glucocorticoids to inflamed joints which may potentially reduce systemic side effects.

Original languageEnglish (US)
Article numberR2
JournalArthritis Research and Therapy
Volume9
DOIs
StatePublished - Mar 1 2007

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hydroxypropyl methacrylate
Dexamethasone
Rheumatoid Arthritis
Joints
Drug Delivery Systems
Therapeutics
Arthritis
Experimental Arthritis
Acidosis
Glucocorticoids
Autoimmune Diseases
Cartilage

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

Cite this

Novel dexamethasone-HPMA copolymer conjugate and its potential application in treatment of rheumatoid arthritis. / Wang, Dong; Miller, Scott C.; Liu, Xin Ming; Anderson, Brian; Wang, X. Sherry; Goldring, Steven R.

In: Arthritis Research and Therapy, Vol. 9, R2, 01.03.2007.

Research output: Contribution to journalArticle

Wang, Dong ; Miller, Scott C. ; Liu, Xin Ming ; Anderson, Brian ; Wang, X. Sherry ; Goldring, Steven R. / Novel dexamethasone-HPMA copolymer conjugate and its potential application in treatment of rheumatoid arthritis. In: Arthritis Research and Therapy. 2007 ; Vol. 9.
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