Document Detail


Controlled release of 2, 3 desulfated heparin exerts its anti-inflammatory activity by effectively inhibiting E-selectin.
MedLine Citation:
PMID:  20540094     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Control of inflammation using appropriate anti-inflammatory agent prevents wound from becoming chronic. Heparin is a heterogeneous mixture of polysaccharide molecules with a mean molecular weight between 12-30 kDa containing 200-300 disaccharide units of glycosaminoglycan chains. Chemical modifications leading to generation of a unique pentasaccharide sequence effectively reduces its anticoagualant activity, while retaining its anti-inflammmatory property. In this study, Standard heparin was partially desulfated to 2, 3 desulfated heparin (2, 3 DSH) and its anti-inflammatory property was determined by assessing its ability to prevent static adhesion of leukocytes to endothelium and clotting assay. The effectiveness of 2, 3 DSH to down regulate E-selectin and key proinflammatory cytokines (IL-1beta and IL-6) was assessed by western blot and immunocytochemistry. These results were compared with commercially available 2-Desulfated Heparin (2DSH) and standard heparin (SH). Finally, a controlled delivery system of 2, 3 DSH was designed using chitosan microspheres and collagen as scaffold. Optimal loading of 2, 3 DSH was achieved and the release kinetics were tuned to follow a controlled release pattern. The steady state concentration of 2, 3 DSH was found to be optimal to elicit anti-inflammatory property and could achieve inhibition of E-selectin expression while unaffecting the normal clotting cascade.
Authors:
T S Ramyaa Lakshmi; N Shanmugasundaram; S Shanmuganathan; K Karthikeyan; J Meenakshi; Mary Babu
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of biomedical materials research. Part A     Volume:  95     ISSN:  1552-4965     ISO Abbreviation:  J Biomed Mater Res A     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-08-26     Completed Date:  2010-12-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101234237     Medline TA:  J Biomed Mater Res A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  118-28     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.
Affiliation:
Biomaterials Division, Central Leather Research Institute, Chennai, Tamil Nadu, India.
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MeSH Terms
Descriptor/Qualifier:
Anti-Inflammatory Agents / chemistry,  pharmacology*
Biological Assay
Blood Coagulation / drug effects
Blotting, Western
Carbohydrate Conformation
Chitosan / pharmacology
Collagen / pharmacology
Cytokines / metabolism
Delayed-Action Preparations
E-Selectin / metabolism*
Endothelial Cells / cytology,  metabolism
Fluoresceins / metabolism
Heparin / analogs & derivatives*,  chemistry,  pharmacology*
Humans
Inflammation Mediators / metabolism
Magnetic Resonance Spectroscopy
Microscopy, Electron, Scanning
Microspheres
Molecular Weight
Partial Thromboplastin Time
Reproducibility of Results
Tissue Scaffolds
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents; 0/Cytokines; 0/Delayed-Action Preparations; 0/E-Selectin; 0/Fluoresceins; 0/Inflammation Mediators; 1461-15-0/fluorexon; 9005-49-6/Heparin; 9007-34-5/Collagen; 9012-76-4/Chitosan

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


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