An azabisphosphonate-capped poly(phosphorhydrazone) dendrimer for the treatment of endotoxin-induced uveitis.
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.
INSERM, U1043, CNRS, U5282, Université de Toulouse, UPS, Centre de Physiopathologie de Toulouse-Purpan, Toulouse F-31300, France.
Séverine
S
Fruchon
Anne-Marie
AM
Caminade
Claire
C
Abadie
Jean-Luc
JL
Davignon
Jean-Marc
JM
Combette
Cédric-Olivier
CO
Turrin
Rémy
R
Poupot
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D050091:Dendrimers / Q000737:chemistry / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D006801:Humans; D006835:Hydrazones / Q000737:chemistry / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D009000:Monocytes / Q000187:drug effects; D063065:Organophosphonates / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D014605:Uveitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D050091:Dendrimers; D006835:Hydrazones; D008070:Lipopolysaccharides; D063065:Organophosphonates; D003907:Dexamethasone