Polyvalent Dendrimer Glucosamine Conjugates Prevent Scar Tissue Formation  

Oleh:

Shaunak, Sunil ; Thomas, Sharyn ; Gianasi, Elisabetta ; Godwin, Antony ; Jones, Emma ; Teo, Ian ; Mireskandari, Kamiar ; Luther, Philip ; Duncan, Ruth ; Patterson, Steve ; Khaw, Peng ; Brocchini, Steve

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Nature Biotechnology: The Science and Business of Biotechnology vol. 22 no. 8 (Agu. 2004), page 977-984.
Topik: MOLECULE; polyvalent dendrimer; glucosamine; tisue formation

Ketersediaan

Perpustakaan Pusat (Semanggi) Nomor Panggil: NN9.1 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

Lihat Detail Induk

Isi artikel

Dendrimers are hyperbranched macromoleculed that can be 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 -1a, MOP-1b, IL-8) and cytokines (TNF-a, IL-1b, IL-6) from human dendritic cells and macrophages but allowed upregulation of the costimulatory molecules CD25, CD80, CD83, CD86. dendrimer glucosamine 6-sulfate blocked fibroblast growth factor-2 mediated endothelial cell proliferation and neoangiogenesis in human matrigel and placentral angiogenesis assays. When dendrimer glucosamine and dredimer 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.

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