Development of a novel anti-inflammatory nanoparticle for the treatment of Acute Lung Injury

急性肺损伤是一种危及生命和使人丧失行为能力的疾病，影响20%的重症监护重症患者。这些患者中约有30-50%会死于这种疾病，许多幸存者可能会因慢性肺部疾病而严重降低生活质量。这不仅对患者本身有重大影响，而且对NHS来说也是一个严重的资源分配问题，因为ICU床位每天的费用超过1800英镑。目前还没有针对这种情况的有效治疗方法，因此迫切需要能够治疗和稳定这种情况的新药。急性肺损伤的特点是肺部炎症的恶性循环，导致免疫细胞不适当地浸润到肺部。我们已经开发出一种治疗这种疾病的潜在方法，这种方法可以通过鼻腔给重症监护室的病人使用，具有有效的抗炎作用。这种治疗方法是一种纳米级的配方，可以与巨噬细胞等免疫细胞表面的免疫抑制受体特异性结合，从而显著减少称为细胞因子的炎症信号分子的产生。因此，在本提案中，我们的目标是通过评估其在一系列ALI临床前模型中的有效性，使这种治疗更接近临床开发。这项工作将告诉我们它的有效性，副作用以及获得显著效果所需的治疗制剂和剂量。

Acute lung injury is a life threatening and incapacitating condition that affects 20% of all critically ill patients in intensive care. Around 30-50% of these sufferers will die from the condition and many survivors can have serious reductions in the quality of the life with chronic lung problems. This not only has a major effect on the patients themselves, but is also a serious resource allocation problem for the NHS as an ICU bed costs in excess of £1800 per day. There is no effective treatments for this condition at this time and therefore new medicines are urgently needed that can deal and stabilise the condition. ALI is characterised by a vicious cycle of inflammation in the lung that leads to inappropriate infiltration of immune cells to the lung. We have developed a potential treatment for this condition that may have the ability to be nasally delivered to patients in intensive care that has potent anti-inflammatory effects. This treatment is a nano-sized formulation that binds specifically to immunosuppressive receptors found on the surface of immune cells such as macrophages, resulting in significant reduction of the production of inflammatory signaling molecules called cytokines. Therefore in this proposal we aim to bring this treatment closer to clinical development by evaluating its effectiveness in a range of preclinical models of ALI. This work will inform us on its effectiveness, side effects and formulation and dosing of the therapeutic required to obtain a significant effect.