Scaling-Up plant based Nanocarriers for BIOpharmaceuticals (SUNBIO)

用于生物制药的植物纳米载体的放大（SUNBIO）

• 批准号: EP/Z53304X/1
• 负责人: Munitta Muthana
• 金额: $ 19.1万
• 依托单位: University of Sheffield
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FZ53304X%2F1
• 关键词: Scaling; Up; plant; based; Nanocarriers

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.

面临的挑战：由于微生物的独特特性，包括其生物相容性和技术，在实验室中很难复制，生物制药以两倍的速度增长。英国需要迅速扩大其生物制药制造能力，以便获得更大的全球市场，并实现创造就业机会和出口的经济益处。“作为药物的虫子”历史上被认为是治疗包括癌症的疾病，包括癌症，激发了下一代癌症患者的治疗选择，尤其是那些患有化学疗法的抗化学疗法，抗化学疗法，耐药性，抗药性，抗药性，转发性疾病。但是，使用“虫子”在内的“虫子”和杀死癌症病毒在内的主要挑战是，它们很容易被免疫系统认识，并在生效之前迅速去除。我们的团队希望通过我们的研究克服这一挑战，以便我们可以为更多患者释放好处，从而使所有癌症都可以接受这些疗法治疗。这些药物的全部潜力只能通过使其对血液中肿瘤的靶向递送在同时绕过人体的防御系统的同时来实现。为此，我们成功地开发了许多用于杀死癌症病毒的纳米载体。由于它们的性质，这些病毒对降解和消除很敏感，但是我们的气泡样颗粒不仅屏蔽了靶向输送，而且包装的方式是维持病毒的可行性和功能的方式 - 首次显示了这一点。合成替代品（例如聚合物）与生物疗法不兼容，这是由于在生产过程中暴露于恶劣条件（热，溶剂，压力）以及被称为高效的效率高度的情况下。利用“设计安全可持续”（SSBD）框架，这是一种自愿方法，可以根据欧洲委员会建议的化学和高级材料的创新过程，我们将扩大生物启发的纳米载体的制造，以成为“诊所准备就绪”。优化这些系统所需的实验范围需要我们在“内部”中开发的高通量微流体。我们的微流体设备可以大规模迅速混合并产生高质量的纳米颗粒封装病毒，并有望超过当前商业设备。现在，我们希望优化我们的设备，并考虑提高混合速度，可重复性，生产力/可扩展性以及降低的成本。Beenfit：到目前为止，由于其体内递送不佳，生物疗法尚未辜负其潜力。在这里，我们提出了一种可持续的解决方案，可以通过在生物启发的纳米颗粒中制定所有癌症来扩展所有癌症的新方式，该方法专门为维持这些敏感生物学剂的功能而设计并提供靶向能力。这个创新的项目与EPSRC核心主题完全一致，以开发我们的生物启发的NP平台可控制，可重现和可扩展的生产，以促进临床翻译并释放生物疗法的功能。这将在不断增长的生物制药市场中提供应用，在该市场中，治疗指数低，免疫原性和缺乏扩展是这些疗法进入的主要障碍。尽管我们使用病毒作为示例，但我们的平台可用于包装任何药物/药物（例如mRNA）进行更广泛的临床应用。