218 Evaluation of an anti-inflammatory dendrimer to topically treat psoriasis

Psoriasis is an auto-immune disease resulting from a chronic and exaggerated inflammation of the skin hyperproliferation keratinocytes. Conventional topical treatments for this disease, such as anti-inflammatory drugs, present low efficiency, systemic administration synthetic drugs or biologic immunomodulators can severe side effects and/or are highly expensive. So, there unmet need to develop new that could provide sustainable therapeutic effects. In study, we evaluated potential efficacy dendrimers treatment psoriasis. Dendrimers hyperbranched perfectly defined macromolecules nanometer size, constituted branches grafted on central core. IMD-006, phosphorus-based dendrimer capped with azabisphosphonate groups, has strong immuno-modulatory towards different immune cell types. We tested IMD-006 in two psoriasis models: imiquimod- induced murine model reconstructed human epidermis (RHE) model, which cocktails pro-inflammatory cytokines used induce psoriasis-associated changes. presented dose-dependent efficacies, significantly reducing lesions histopathological changes associated Moreover, show rapidly taken up by keratinocytes 2D culture, decreasing their proliferation increasing differentiation. mitochondria, increased mitochondrial ROS production ultimately lysosomal degradation these organelles. Therefore, anti-psoriatic effect is, at least part, result direct Our results demonstrate good candidates broad multiple types involved development progression disease.