| Ionic complex systems based on hyaluronic acid and PEGylated TNF-related apoptosis-inducing ligand for treatment of rheumatoid arthritis. | |
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MedLine Citation:
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PMID: 20813405 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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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 |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Biomaterials Volume: 31 ISSN: 1878-5905 ISO Abbreviation: Biomaterials Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-10-04 Completed Date: 2011-01-18 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8100316 Medline TA: Biomaterials Country: England |
Other Details:
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Languages: eng Pagination: 9057-64 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Ltd. All rights reserved. |
Affiliation:
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Department of Chemical Engineering, College of Engineering, Kyung Hee University, Gyeonggi-do 449-701, South Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Arthritis, Rheumatoid / blood, drug therapy* Cell Proliferation / drug effects Cytokines / blood Diffusion / drug effects Humans Hyaluronic Acid / chemistry, pharmacology, therapeutic use* Ions Kinetics Knee Joint / drug effects, pathology Mice Mice, Nude Microscopy, Fluorescence Nanostructures / therapeutic use Particle Size Polyethylene Glycols / therapeutic use* Spleen / cytology TNF-Related Apoptosis-Inducing Ligand / pharmacokinetics, pharmacology, therapeutic use* Tissue Distribution / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/Ions; 0/Polyethylene Glycols; 0/TNF-Related Apoptosis-Inducing Ligand; 9004-61-9/Hyaluronic Acid |
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