The arthrotropism of macromolecules in adjuvant-induced arthritis rat model: A preliminary study

Dong Wang, Scott C. Miller, Monika Sima, Dennis Parker, Henry Buswell, K. Craig Goodrich, Pavla Kopečková, Jindřich Kopeček

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Purpose. To study the accumulation of macromolecules into the arthritic joints and the possible applications of such phenomenon. Methods. The accumulation of plasma albumin in the joints of adjuvant-induced arthritis (AIA) rat model was first visualized with Evans blue injection. A N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer contrast agent was then synthesized and injected into the AIA rats to allow qualitative examination of biodistribution and pharmacokinetics of the injected macromolecule with magnetic resonance imaging (MRI). Vital organs and the diseased joints were isolated and examined histologically to correlate with the MRI findings. Results. Deep blue color developed around the arthritic joints of the AIA rat a few hours after the injection of Evans blue. MR imaging of the AIA rats injected with polymer contrast agent demonstrated a gradual but very strong accumulation of the injected polymer in the arthritic joints, which lasted for 1∼2 days. Observed differences in the concentration of the injected polymer in the joints correlated with disease severity as assessed histologically. Conclusions. Profound arthrotropism of macromolecules in the AIA rat model was demonstrated with various imaging tools. These observations should help in the conceptual and practical design of novel macromolecular delivery systems for the imaging and treatment of rheumatoid arthritis.

Original languageEnglish (US)
Pages (from-to)1741-1749
Number of pages9
JournalPharmaceutical Research
Volume21
Issue number10
DOIs
StatePublished - Oct 1 2004

Keywords

  • arthrotropism
  • drug delivery
  • macromolecular therapy
  • macromolecule
  • magnetic resonance imaging (MRI)
  • rheumatoid arthritis

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

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    Wang, D., Miller, S. C., Sima, M., Parker, D., Buswell, H., Goodrich, K. C., Kopečková, P., & Kopeček, J. (2004). The arthrotropism of macromolecules in adjuvant-induced arthritis rat model: A preliminary study. Pharmaceutical Research, 21(10), 1741-1749. https://doi.org/10.1023/B:PHAM.0000045232.18134.e9