Scaling-Up plant based Nanocarriers for BIOpharmaceuticals (SUNBIO)

挑战：生物制药的增长速度是传统制药的两倍，这是因为微生物的独特属性，包括它们的生物兼容性和无法在实验室轻松复制的技术。英国需要迅速扩大其生物制药制造能力，以进入更大的全球市场份额，并实现创造就业和出口的经济效益。历史上，“虫子即药物”被视为治疗包括癌症在内的疾病，这正在激励癌症患者的下一代治疗选择，特别是那些患有化疗耐药、复发或转移性疾病的患者。然而，使用包括细菌和致癌病毒在内的“细菌”的一个主要挑战是，它们很容易被免疫系统识别，并在它们生效之前迅速消除。我们的团队希望通过我们的研究来克服这一挑战，这样我们就可以为更多的患者带来好处，允许所有癌症都可以用这些疗法治疗。这些药物的全部潜力只有通过使它们能够定向递送到血液中的肿瘤，同时绕过身体的防御系统才能实现。为了做到这一点，我们已经成功地开发了一些用于抗癌病毒的纳米载体。由于它们的性质，这些病毒对降解和消除很敏感，然而我们的泡沫状颗粒不仅保护它们进行靶向传递，而且包装的方式保持了病毒的生存能力和功能-这是第一次显示这一点。合成替代品(如聚合物)在生产过程中暴露在恶劣的条件(热、溶剂、压力)下，并且被认为效率极低，与生物疗法不相容。目的：这里，我们重点介绍来自自然来源(如植物)的无毒、生物相容、可持续和可生物降解的材料。利用欧盟委员会建议的“安全和可持续的设计”(SSBD)框架，这是一种指导化学品和先进材料创新过程的自愿方法，我们将扩大我们的生物灵感纳米载体的制造，使其“为临床准备好”。优化这些系统所需的实验范围需要高通量的微流体，这是我们在内部开发的。我们的微流体设备可以大规模快速混合和生产高质量的纳米颗粒包裹的病毒，并承诺超越当前的商业设备。我们现在想要优化我们的设备，并考虑提高混合速度、重复性、生产率/可扩展性以及降低成本。BENEFIT：到目前为止，生物疗法由于在体内的传递能力差，没有发挥出它们的潜力。在这里，我们提出了一个可持续的解决方案，通过在生物启发的纳米颗粒中形成新的治疗方式来扩大所有癌症的治疗范围，这些纳米颗粒专门设计来保持这些敏感生物制剂的功能并提供靶向能力。这一创新项目完全符合EPSRC的核心主题，即开发一条管道，用于我们的生物灵感NP平台的可控、可重复和可扩展的生产，以促进临床翻译并释放生物疗法的力量。这将在不断增长的生物制药市场得到应用，在这些市场，治疗指数低、免疫原性和缺乏扩大规模是这些疗法进入的主要障碍。虽然我们使用病毒作为样本，但我们的平台可以用于包装任何药物/试剂(例如，信使核糖核酸)，以便更广泛的临床应用。

THE CHALLENGE: Biopharmaceuticals are growing at a rate double of traditional pharma owing to the unique properties of microorganisms including their biocompatibility and technology that cannot be easily replicated in the lab. The UK needs to rapidly expand its biopharmaceutical manufacturing capacity in order to access a greater fraction of the global market and realise the economic benefits of job creation and exports."Bugs as drugs" have been seen historically to treat diseases including cancer which is inspiring the next generation of treatment options for cancer patients, particularly those with chemotherapy-resistant, recurrent, or metastatic disease. However, a major challenge for use of "bugs" including bacteria and cancer-killing viruses is they are readily recognised by the immune system and rapidly removed before they can take effect. Our team wants to overcome this challenge through our research so that we can unlock the benefits for more patients, allowing all cancer to be treated with these therapies. The full potential of these medicines can only be realised by enabling their targeted delivery to tumours within the bloodstream whilst simultaneously bypassing the body's defence systems. To do this, we have successfully developed a number of nanocarriers for cancer-killing viruses. Due to their nature, these viruses are sensitive to degradation and elimination, however our bubble-like particles not only shield them for targeted delivery, but the packaging is done in a way that maintains the viruses viability and functionality - the first time this has been shown. Synthetic alternatives (e.g. polymers) are incompatible with biological therapies due to exposure to harsh conditions (heat, solvents, pressure) during production as well as being known as highly inefficient.OBJECTIVES: Here, we focus on materials derived from natural sources (e.g. plants) that are non-toxic, biocompatible, sustainable and biodegradable. Utilising the 'safe and sustainable by design' (SSbD) framework, a voluntary approach to guide the innovation process for chemicals and advanced materials as recommended by the European Commission, we will scale-up the manufacture of our bioinspired nanocarriers to be 'clinic ready'. The scope of experiments required to optimise these systems requires high throughput microfluidics which we have developed 'in house'. Our microfluidics device can rapidly mix and produce high quality nanoparticle encapsulated viruses at large scale with the promise to outperform current commercial devices. We now want to optimise our device and consider improved mixing speed, reproducibility, productivity/scalability as well as reduced cost.BENEFIT: So far, biological therapies have not lived up to their potential due to their poor delivery in the body. Here we present a sustainable solution to scale up new modalities for the treatment of all cancers by formulating them within bioinspired nanoparticles, specifically designed to maintain the functionality of these sensitive biological agents and provide targeting capabilities. This innovative project fully aligns with the EPSRC core theme for the development of a pipeline for controllable, reproducible, and scalable production of our bioinspired NP platforms to facilitate clinical translation and unlock the power of biological therapies. This will have applications across the growing biopharma market where low therapeutic index, immunogenicity and lack of scale-up are major barriers to entry for these therapies. Whilst we use viruses as an exemplar, our platforms can be used to package any drug/agent (e.g mRNA) for wider clinical application.