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An Azabisphosphonate-Capped Poly(phosphorhydrazone) Dendrimer for the Treatment of Endotoxin-Induced Uveitis
INSERM, U1043, CNRS, U5282, Université de Toulouse, UPS, Centre de Physiopathologie de Toulouse-Purpan, Toulouse F-31300, France
CNRS, LCC (Laboratoire de Chimie de Coordination) 205 route de Narbonne, BP 44099, F-31077 Toulouse cedex 4, France
Solid Drug Development SA, 8 rue John Grasset, Geneva CH-1205, Switzerland
* Authors to whom correspondence should be addressed.
Received: 15 July 2013; in revised form: 26 July 2013 / Accepted: 1 August 2013 / Published: 5 August 2013
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
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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.
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(8):9305-9316.
Fruchon, Séverine; Caminade, Anne-Marie; Abadie, Claire; Davignon, Jean-Luc; Combette, Jean-Marc; Turrin, Cédric-Olivier; Poupot, Rémy. 2013. "An Azabisphosphonate-Capped Poly(phosphorhydrazone) Dendrimer for the Treatment of Endotoxin-Induced Uveitis." Molecules 18, no. 8: 9305-9316.