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Controlled release of 2, 3 desulfated heparin exerts its anti‐inflammatory activity by effectively inhibiting E‐selectin
Author(s) -
Lakshmi T. S. Ramyaa,
Shanmugasundaram N.,
Shanmuganathan S.,
Karthikeyan K.,
Meenakshi J.,
Babu Mary
Publication year - 2010
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.32791
Subject(s) - heparin , proinflammatory cytokine , glycosaminoglycan , materials science , western blot , clotting time , p selectin , inflammation , pharmacology , biochemistry , microbiology and biotechnology , medicine , platelet activation , platelet , immunology , biology , gene
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‐1β 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. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.