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, Kwang Meyung Kim, Ick Chan Kwon, Kang Choon Lee, Jae Hyung Park

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

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
JournalBiomaterials
Volume31
Issue number34
DOIs
Publication statusPublished - 2010 Dec 1
Externally publishedYes

Fingerprint

TNF-Related Apoptosis-Inducing Ligand
Hyaluronic acid
Cell death
Hyaluronic Acid
Large scale systems
Rheumatoid Arthritis
Polyethylene glycols
Ligands
Therapeutics
Collagen
Tumor Necrosis Factor-alpha
PEGylated tumor necrosis factor-related apoptosis-inducing ligand
Optical Devices
Histology
Experimental Arthritis
Optical Imaging
Therapeutic Uses
Subcutaneous Injections
Bioactivity
Imaging systems

Keywords

  • Hyaluronic acid
  • Nanocomplex
  • PEG-TRAIL
  • Protein delivery
  • Rheumatoid arthritis

ASJC Scopus subject areas

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

Cite this

Ionic complex systems based on hyaluronic acid and PEGylated TNF-related apoptosis-inducing ligand for treatment of rheumatoid arthritis. / Kim, Yu Jeong; Chae, Su Young; Jin, Cheng Hao; Sivasubramanian, M.; Son, Sohee; Choi, Ki Young; Jo, Dong Gyu; Kim, Kwang Meyung; Kwon, Ick Chan; Lee, Kang Choon; Park, Jae Hyung.

In: Biomaterials, Vol. 31, No. 34, 01.12.2010, p. 9057-9064.

Research output: Contribution to journalArticle

Kim, YJ, Chae, SY, Jin, CH, Sivasubramanian, M, Son, S, Choi, KY, Jo, DG, Kim, KM, Kwon, IC, Lee, KC & Park, JH 2010, 'Ionic complex systems based on hyaluronic acid and PEGylated TNF-related apoptosis-inducing ligand for treatment of rheumatoid arthritis', Biomaterials, vol. 31, no. 34, pp. 9057-9064. https://doi.org/10.1016/j.biomaterials.2010.08.015
Kim, Yu Jeong ; Chae, Su Young ; Jin, Cheng Hao ; Sivasubramanian, M. ; Son, Sohee ; Choi, Ki Young ; Jo, Dong Gyu ; Kim, Kwang Meyung ; Kwon, Ick Chan ; Lee, Kang Choon ; Park, Jae Hyung. / Ionic complex systems based on hyaluronic acid and PEGylated TNF-related apoptosis-inducing ligand for treatment of rheumatoid arthritis. In: Biomaterials. 2010 ; Vol. 31, No. 34. pp. 9057-9064.
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abstract = "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.",
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AU - Son, Sohee

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AU - Jo, Dong Gyu

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