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

Title
Ionic complex systems based on hyaluronic acid and pegylated TNF-related apoptosis-inducing ligand for treatment of rheumatoid arthritis
Authors
김유정채수영진정호M. Sivasubramanian손소희최기영조동규김광명권익찬이강춘박재형
Keywords
Protein delivery; PEGeTRAIL; Rheumatoid arthritis; Nanocomplex; Hyaluronic acid
Issue Date
2010-12
Publisher
Biomaterials
Citation
VOL 31, NO 34, 9057-9064
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)ederivatized TRAIL (PEGeTRAIL) formed by N-terminal specific PEGylation. The nanocomplexes were prepared by simply mixing the positively charged PEGeTRAIL and negatively charged HA, and showed negligible loss of bioactivity compared with the PEGeTRAIL. The in vivo biodistribution and diffusion kinetics of Cy5.5-labeled PEGeTRAIL in mice were observed using a near-infrared optical imaging system after subcutaneous injection of three different formulations: PEGeTRAIL in phosphatee buffered saline (PBS, pH 7.4), nanocomplex in PBS, or nanocomplex in 1% HA solution. The results suggested that PEGeTRAIL 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 PEGe TRAIL, with the order of nanocomplex in 1% HA > nanocomplex in PBS > PEGeTRAIL in PBS. In addition, sustained delivery of PEGeTRAIL 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/PEGeTRAIL nanocomplex formulations are promising therapeutic modalities for the treatment of RA.
URI
http://pubs.kist.re.kr/handle/201004/38236
ISSN
0142-9612
Appears in Collections:
KIST Publication > Article
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