Controlled release of 2, 3 desulfated heparin exerts its anti-inflammatory activity by effectively inhibiting E-selectin.
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.
Biomaterials Division, Central Leather Research Institute, Chennai, Tamil Nadu, India.
T S Ramyaa
TS
Lakshmi
N
N
Shanmugasundaram
S
S
Shanmuganathan
K
K
Karthikeyan
J
J
Meenakshi
Mary
M
Babu
D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D001681:Biological Assay; D001777:Blood Coagulation / Q000187:drug effects; D015153:Blotting, Western; D002236:Carbohydrate Conformation; D048271:Chitosan / Q000494:pharmacology; D003094:Collagen / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D003692:Delayed-Action Preparations; D019040:E-Selectin / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005452:Fluoresceins / Q000378:metabolism; D006493:Heparin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D008970:Molecular Weight; D010314:Partial Thromboplastin Time; D015203:Reproducibility of Results; D054457:Tissue Scaffolds
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D003692:Delayed-Action Preparations; D019040:E-Selectin; D005452:Fluoresceins; D018836:Inflammation Mediators; D006493:Heparin; D003094:Collagen; D048271:Chitosan; C007740:fluorexon