An Anti-Inflammatory Poly(PhosphorHydrazone) Dendrimer Capped with AzaBisPhosphonate Groups to Treat Psoriasis

一种抗炎聚(磷腙)树枝状聚合物,以氮杂双膦酸酯基团封端,用于治疗牛皮癣

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作者:Ranime Jebbawi, Abdelouahd Oukhrib, Emily Clement, Muriel Blanzat, Cédric-Olivier Turrin, Anne-Marie Caminade, Eric Lacoste, Séverine Fruchon, Rémy Poupot

Abstract

Dendrimers are nanosized, arborescent macromolecules synthesized in a stepwise fashion with attractive degrees of functionality and structure definition. This is one of the reasons why they are widely used for biomedical applications. Previously, we have shown that a poly(phosphorhydrazone) (PPH) dendrimer capped with anionic azabisphosphonate groups (so-called ABP dendrimer) has immuno-modulatory and anti-inflammatory properties towards human immune cells in vitro. Thereafter, we have shown that the ABP dendrimer has a promising therapeutic efficacy to treat models of acute and chronic inflammatory disorders in animal models. In these models, the active pharmaceutical ingredient was administered systematically (intravenous and oral administrations), but also loco-regionally in the vitreous tissue. Herein, we assessed the therapeutic efficacy of the ABP dendrimer in the preclinical mouse model of psoriasis induced by imiquimod. The ABP dendrimer was administered in phosphate-buffered saline solution via either systemic injection or topical application. We show that the topical application enabled the control of both the clinical and histopathological scores, and the control of the infiltration of macrophages in the skin of treated mice.

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