Ionic complex systems based on hyaluronic acid and PEGylated TNF-related apoptosis-inducing ligand for treatment of rheumatoid arthritis

Yu Jeong Kim, Su Young Chae, Cheng Hao Jin, M. Sivasubramanian, Sohee Son, Ki Young Choi, Dong Gyu Jo, Kwangmeyung Kim, Ick Chan Kwon, Kang Choon Lee, Jae Hyung Park

Research output: Contribution to journalArticlepeer-review

57 Citations (Scopus)


The clinical applications of tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL), an emerging therapeutic protein for cancer and rheumatoid arthritis (RA), are limited by its instability and short biological half-life. In this study, efficient therapeutic modalities for RA treatment were developed in the form of nano-sized complexes (nanocomplexes) based on hyaluronic acid (HA) and polyethylene glycol (PEG)-derivatized TRAIL (PEG-TRAIL) formed by N-terminal specific PEGylation. The nanocomplexes were prepared by simply mixing the positively charged PEG-TRAIL and negatively charged HA, and showed negligible loss of bioactivity compared with the PEG-TRAIL. The in vivo biodistribution and diffusion kinetics of Cy5.5-labeled PEG-TRAIL in mice were observed using a near-infrared optical imaging system after subcutaneous injection of three different formulations: PEG-TRAIL in phosphate-buffered saline (PBS, pH 7.4), nanocomplex in PBS, or nanocomplex in 1% HA solution. The results suggested that PEG-TRAIL is released slowly in vivo from the nanocomplex in 1% HA. Experiments in a collagen-induced arthritis mouse model demonstrated that the magnitudes of therapeutic effects, as judged by clinical scores and histology, were significantly enhanced by the sustained delivery of PEG-TRAIL, with the order of nanocomplex in 1% HA > nanocomplex in PBS > PEG-TRAIL in PBS. In addition, sustained delivery of PEG-TRAIL from the nanocomplex in 1% HA resulted in significant reduction of serum inflammatory cytokines and collagen-specific antibodies that are responsible for the pathogenesis of RA. These results imply that HA/PEG-TRAIL nanocomplex formulations are promising therapeutic modalities for the treatment of RA.

Original languageEnglish
Pages (from-to)9057-9064
Number of pages8
Issue number34
Publication statusPublished - 2010 Dec

Bibliographical note

Funding Information:
This work was supported by the Ministry of Education, Science and Technology (20090081871 and 20100015804), the National R&D Program for Cancer Control (0920120) and the Korea Health 21 R&D Project (A062254) of MIHWAF, and BioImaging Research Center at GIST, Republic of Korea.


  • Hyaluronic acid
  • Nanocomplex
  • Protein delivery
  • Rheumatoid arthritis

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Ceramics and Composites
  • Biomaterials
  • Mechanics of Materials


Dive into the research topics of 'Ionic complex systems based on hyaluronic acid and PEGylated TNF-related apoptosis-inducing ligand for treatment of rheumatoid arthritis'. Together they form a unique fingerprint.

Cite this