Polyvalent dendrimer glucosamine conjugates prevent scar tissue formation

Shaunak, S., Thomas, S., Gianasi, E., Godwin, A., Jones, E., Teo, I., Mireskandari, K., Luthert, P., Duncan, R., Patterson, S., Khaw, P.T. and Brocchini, S. (2004) Polyvalent dendrimer glucosamine conjugates prevent scar tissue formation. Nature Biotechnology, 22 (8). p. 977. 10.1038/nbt995.

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DOI: 10.1038/nbt995

Abstract

Dendrimers are hyperbranched macromolecules that can be chemically synthesized to have precise structural characteristics. We used anionic, polyamidoamine, generation 3.5 dendrimers to make novel water-soluble conjugates of D(+)-glucosamine and D(+)-glucosamine 6-sulfate with immuno-modulatory and antiangiogenic properties respectively. Dendrimer glucosamine inhibited Toll-like receptor 4–mediated lipopolysaccharide induced synthesis of pro-inflammatory chemokines (MIP-1, MIP-1, IL-8) and cytokines (TNF-, IL-1, IL-6) from human dendritic cells and macrophages but allowed upregulation of the costimulatory molecules CD25, CD80, CD83 and CD86. Dendrimer glucosamine 6-sulfate blocked fibroblast growth factor-2 mediated endothelial cell proliferation and neoangiogenesis in human Matrigel and placental angiogenesis assays. When dendrimer glucosamine and dendrimer glucosamine 6-sulfate were used together in a validated and clinically relevant rabbit model of scar tissue formation after glaucoma filtration surgery, they increased the long-term success of the surgery from 30% to 80% (P = 0.029). We conclude that synthetically engineered macromolecules such as the dendrimers described here can be tailored to have defined immuno-modulatory and antiangiogenic properties, and they can be used synergistically to prevent scar tissue formation.

Item Type:Article
Departments, units and centres:Department of Pharmaceutics > Department of Pharmaceutics
ID Code:2138
Journal or Publication Title:Nature Biotechnology
Deposited By:Library Staff
Deposited On:26 May 2011 11:14
Last Modified:26 May 2011 11:14

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