Cocrystal-enabled Inhaled Therapy for Idiopathic Pulmonary Fibrosis

该项目将评估吸入递送共晶体使能的已知药物以在体内治疗特发性肺纤维化（IPF）的可行性。IPF的第一种疗法-一种具有高死亡率（50%在诊断后2-3年内死亡 *）的增长性疾病（5000名英国患者诊断/年 *）于2014年获得批准（吡非尼酮和诺维信）。这些新疗法不能阻止疾病进展，而且口服治疗有非常不希望的副作用。该项目旨在表明，通过将更有效的药物直接输送到肺部，可以提高治疗效果，而不会产生副作用。创新点有四个：1。吸入治疗IPF是一种新概念，能够将药物直接递送至需要的部位，提高疗效并最大限度地减少不良药物暴露。>80%的患者有呼吸功能，可以使用干粉吸入器（DPI）**.活性成分将是曲尼司特-一种日本口服哮喘药，具有很强的安全性。曲尼司特也被证实是一种抗纤维化药物，因此在IPF中具有新的潜力。共晶技术可以改善药物分子的关键物理性质。曲尼司特不溶性共晶技术将改善肺部溶解度和生物分布，最大限度地提高性能。这种共晶应用将是第一次用于吸入。4.博来霉素是公认的IPF疾病模型，但有局限性。肺切片培养（LSC）模型解决了它的问题，减少了使用的动物数量，但验证较少。未使用相同药物对2种模型进行比较。这种新的组合方法将进一步验证结果和LSC模型为未来的研究.用于DPI体内递送的过程和装置是有限的，并且比另一种方法更少验证。该研究将制定可靠的程序，以调查与设想的最终产品相匹配的交付概念。** G.教授詹金斯

The project will evaluate the feasibility of inhaled delivery of a cocrystal-enabled known drugto treat idiopathic pulmonary fibrosis (IPF) in-vivo.The 1st therapies for IPF - a growing disease (5000 UK patients diagnosed/year*) with highmortality (50% die in 2-3 years of diagnosis*) were approved in 2014 (Pirfenidone &Nintedanib). These new therapies do not prevent disease progression and as oral treatmentshave highly undesirable side-effects. The project aims to show that by delivering a moreeffective drug directly to the lung, the efficacy of treatment can be increased without sideeffects. There are 4 innovative aspects:1. Inhalation for IPF is a novel concept & enables drug delivery direct to the site of need,increasing efficacy and minimising undesirable drug exposure. >80% of patients have thelung function to use a dry powder inhaler (DPI)**.2. The active ingredient will be Tranilast – a Japanese oral asthma drug with a strong safetyprofile. Tranilast is also well validated as an anti-fibrotic agent and therefore has new potentialfor use in IPF.3. Cocrystal technology can improve key physical properties for drug molecules. Tranilast ishighly insoluble and cocrystal technology will improve lung solubility & biodistribution,maximising performance. This cocrystal application would be a 1st for inhalation.4. Bleomycin is an accepted IPF disease model but has limitations. The Lung Slice Culture(LSC) model addresses its problems & reduces the number of animals used, but is lessvalidated. The 2 models have not been compared using the same drug. This novel combinedapproach will further validate both the result and the LSC model for future studies.5. The processes & devices used for DPI delivery in-vivo are limited and less validated thanother methods. The study will develop reliable processes to investigate the delivery conceptthat matches the envisaged end product (DPI).*NHS data**Prof. G. Jenkins