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首页> 外文期刊>Biomaterials >Suppression of inflammation in a mouse model of rheumatoid arthritis using targeted lipase-labile fumagillin prodrug nanoparticles
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Suppression of inflammation in a mouse model of rheumatoid arthritis using targeted lipase-labile fumagillin prodrug nanoparticles

机译：使用靶向脂肪酶不稳定的烟曲霉素前药纳米颗粒抑制类风湿关节炎小鼠模型中的炎症

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摘要

Nanoparticle-based therapeutics are emerging technologies that have the potential to greatly impact the treatment of many human diseases. However, drug instability and premature release from the nanoparticles during circulation currently preclude clinical translation. Herein, we use a lipase-labile (Sn 2) fumagillin prodrug platform coupled with a unique lipid surface-to-surface targeted delivery mechanism, termed contact-facilitated drug delivery, to counter the premature drug release and overcome the inherent photo-instability of fumagillin, an established anti-angiogenic agent. We show that α vβ 3-integrin targeted fumagillin prodrug nanoparticles, administered at 0.3 mg of fumagillin prodrug/kg of body weight suppress the clinical disease indices of KRN serum-mediated arthritis in a dose-dependent manner when compared to treatment with the control nanoparticles with no drug. This study demonstrates the effectiveness of this lipase-labile prodrug nanocarrier in a relevant preclinical model that approximates human rheumatoid arthritis. The lipase-labile prodrug paradigm offers a translatable approach that is broadly applicable to many targeted nanosystems and increases the translational potential of this platform for many diseases.
机译：基于纳米粒子的疗法是新兴技术，可能极大地影响许多人类疾病的治疗。然而，药物不稳定性和在循环过程中从纳米颗粒中过早释放目前阻止了临床翻译。在本文中，我们使用脂酶不稳定（Sn 2）的富马洁林前药平台，并结合独特的脂质表面对表面靶向递送机制，称为接触促进药物递送，以对抗过早释放的药物并克服内在的光不稳定性。烟曲霉素，一种成熟的抗血管生成剂。我们显示，与对照纳米粒子治疗相比，以0.3 mg的烟曲霉素前药/ kg体重给药的αvβ3-整联蛋白靶向的烟曲霉素前药纳米颗粒以剂量依赖的方式抑制了KRN血清介导的关节炎的临床疾病指数。没有毒品。这项研究证明了这种脂酶不稳定的前药纳米载体在近似于人类类风湿关节炎的相关临床前模型中的有效性。脂酶不稳定的前药范例提供了可广泛应用于许多目标纳米系统的可翻译方法，并增加了该平台对多种疾病的翻译潜力。

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