INSERM, U1043, CNRS, U5282, Université de Toulouse, UPS, Centre de Physiopathologie de Toulouse-Purpan, F-31300 Toulouse, France.
CNRS, UMR 5623, Université de Toulouse, UPS, Laboratoire des Interactions Moléculaires et Réactivité Chimique et Photochimique, IMRCP, 118 route de Narbonne, CEDEX 9, F-31062 Toulouse, France.
Biomolecules. 2020 Jun 23;10(6):949. doi: 10.3390/biom10060949.
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.
树突状聚合物是纳米级的、树枝状的大分子，通过逐步合成，具有吸引人的功能和结构定义程度。这就是它们被广泛用于生物医学应用的原因之一。此前，我们已经表明，带有阴离子氮杂双膦酸酯基团的聚（磷酰肼）（PPH）树突（所谓的 ABP 树突）具有体外对人免疫细胞的免疫调节和抗炎特性。此后，我们已经表明，ABP 树突在治疗动物模型中的急性和慢性炎症性疾病方面具有有前途的治疗效果。在这些模型中，将活性药物成分系统地（静脉内和口服给药），但也局部递送至玻璃体内组织。在此，我们评估了 ABP 树突在咪喹莫特诱导的银屑病的临床前小鼠模型中的治疗效果。ABP 树突通过全身注射或局部应用磷酸盐缓冲盐水溶液给药。我们表明，局部应用能够控制临床和组织病理学评分，并控制治疗小鼠皮肤中巨噬细胞的浸润。
