Document Detail


Ionic complex systems based on hyaluronic acid and PEGylated TNF-related apoptosis-inducing ligand for treatment of rheumatoid arthritis.
MedLine Citation:
PMID:  20813405     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biomaterials     Volume:  31     ISSN:  1878-5905     ISO Abbreviation:  Biomaterials     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-10-04     Completed Date:  2011-01-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8100316     Medline TA:  Biomaterials     Country:  England    
Other Details:
Languages:  eng     Pagination:  9057-64     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ltd. All rights reserved.
Affiliation:
Department of Chemical Engineering, College of Engineering, Kyung Hee University, Gyeonggi-do 449-701, South Korea.
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MeSH Terms
Descriptor/Qualifier:
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:
0/Cytokines; 0/Ions; 0/Polyethylene Glycols; 0/TNF-Related Apoptosis-Inducing Ligand; 9004-61-9/Hyaluronic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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