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Molecules 2013, 18(8), 9305-9316; doi:10.3390/molecules18089305
Article

An Azabisphosphonate-Capped Poly(phosphorhydrazone) Dendrimer for the Treatment of Endotoxin-Induced Uveitis

1
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2
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3
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1
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3
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2,*  and 1,*
1 INSERM, U1043, CNRS, U5282, Université de Toulouse, UPS, Centre de Physiopathologie de Toulouse-Purpan, Toulouse F-31300, France 2 CNRS, LCC (Laboratoire de Chimie de Coordination) 205 route de Narbonne, BP 44099, F-31077 Toulouse cedex 4, France 3 Solid Drug Development SA, 8 rue John Grasset, Geneva CH-1205, Switzerland
* Authors to whom correspondence should be addressed.
Received: 15 July 2013 / Revised: 26 July 2013 / Accepted: 1 August 2013 / Published: 5 August 2013
(This article belongs to the Special Issue Dendrimers in Medicine and Biotechnology)
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Abstract

Over the last decade, different types of dendrimers have shown anti-inflammatory properties in their own right. In particular, we have shown that poly(phosphorhydrazone) (PPH) dendrimers are able to foster an efficient anti-inflammatory response in human monocytes and can resolve the main physiopathological features of chronic arthritis in mice at 1 mg/kg. Here we afford new insights into the therapeutic potential of an azabisphosphonate-capped dendrimer (dendrimer ABP). We have challenged its anti-inflammatory and immuno-modulatory properties in a robust rat model of acute uveitis induced by lipopolysaccharide (LPS). We show that dendrimer ABP at 2 µg/eye is as efficient as the “gold standard” dexamethasone at 20 µg/eye. We have demonstrated that the effect of dendrimer ABP is mediated at least through an increase of the production of the anti-inflammatory Interleukin(IL)-10 cytokine.
Keywords: PPH [poly(phosphorhydrazone)] dendrimer; anti-inflammatory; uveitis; toxicity PPH [poly(phosphorhydrazone)] dendrimer; anti-inflammatory; uveitis; toxicity
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Fruchon, S.; Caminade, A.-M.; Abadie, C.; Davignon, J.-L.; Combette, J.-M.; Turrin, C.-O.; Poupot, R. An Azabisphosphonate-Capped Poly(phosphorhydrazone) Dendrimer for the Treatment of Endotoxin-Induced Uveitis. Molecules 2013, 18, 9305-9316.

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