Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.jconrel.2012.09.013
Title: Orally active desulfated low molecular weight heparin and deoxycholic acid conjugate, 6ODS-LHbD, suppresses neovascularization and bone destruction in arthritis
Authors: Hwang, S.R.
Seo, D.-H.
Al-Hilal, T.A.
Jeon, O.-C.
Kang, J.H.
Kim, S.-H.
Kim, H.S.
Chang, Y.-T. 
Kang, Y.M.
Yang, V.C.
Byun, Y.
Keywords: Angiogenesis
Deoxycholic acid
Heparin
O-desulfation
Oral delivery
Rheumatoid arthritis
Issue Date: 10-Nov-2012
Citation: Hwang, S.R., Seo, D.-H., Al-Hilal, T.A., Jeon, O.-C., Kang, J.H., Kim, S.-H., Kim, H.S., Chang, Y.-T., Kang, Y.M., Yang, V.C., Byun, Y. (2012-11-10). Orally active desulfated low molecular weight heparin and deoxycholic acid conjugate, 6ODS-LHbD, suppresses neovascularization and bone destruction in arthritis. Journal of Controlled Release 163 (3) : 374-384. ScholarBank@NUS Repository. https://doi.org/10.1016/j.jconrel.2012.09.013
Abstract: The regulation of angiogenesis is an interesting area to consider for novel therapeutic approaches to rheumatoid arthritis (RA). Chemically modified heparins have been developed as possible candidates for angiogenesis inhibitor; however, they have a major clinical drawback in exhibiting poor oral bioavailability. Here, orally absorbable O-desulfated low molecular weight heparin (ODS-LMWH) derivatives were newly synthesized by conjugating 2-O- or 6-O-desulfated LMWH with deoxycholic acid (DOCA) or bisDOCA (a dimer of DOCA), and their physicochemical properties, antiangiogenic potency and pharmacokinetic profiles were assessed. After selecting the best candidate among those derivatives, its therapeutic efficacy on arthritis was investigated in a murine collagen antibody-induced arthritis (CAIA) model. ODS-LMWH derivatives significantly inhibited the capillary-like tube formation of human umbilical vein endothelial cells (HUVECs) and basic fibroblast growth factor (bFGF)-induced angiogenesis in the Matrigel plug assay. Among all the compounds, 6ODS-LHbD showed the highest oral bioavailability in rats (19.3%). In the CAIA mouse model, 6ODS-LHbD (10 mg/kg, p.o., S.I.D.) significantly inhibited neovascularization in the joint, the increase of hind-paw thickness, and the structural damage in the bone. Therefore, 6ODS-LHbD would be a promising candidate for an orally active drug for the treatment of RA. © 2012 Elsevier B.V. All rights reserved.
Source Title: Journal of Controlled Release
URI: http://scholarbank.nus.edu.sg/handle/10635/76695
ISSN: 01683659
DOI: 10.1016/j.jconrel.2012.09.013
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

16
checked on Dec 7, 2018

WEB OF SCIENCETM
Citations

14
checked on Nov 21, 2018

Page view(s)

34
checked on Dec 8, 2018

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.