An azabisphosphonate-capped poly(phosphorhydrazone) dendrimer for the treatment of endotoxin-induced uveitis

Molecules. 2013 Aug 5;18(8):9305-16. doi: 10.3390/molecules18089305.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Dendrimers / chemistry
  • Dendrimers / pharmacology*
  • Dexamethasone / pharmacology
  • Humans
  • Hydrazones / chemistry
  • Hydrazones / pharmacology
  • Lipopolysaccharides / toxicity
  • Mice
  • Monocytes / drug effects
  • Organophosphonates / chemistry
  • Organophosphonates / pharmacology*
  • Rats
  • Uveitis / chemically induced
  • Uveitis / drug therapy*
  • Uveitis / metabolism

Substances

  • Anti-Inflammatory Agents
  • Dendrimers
  • Hydrazones
  • Lipopolysaccharides
  • Organophosphonates
  • Dexamethasone