Molecular strategy for developing instant nanomedicine

开发即时纳米药物的分子策略

• 批准号: EP/Z532952/1
• 负责人: Hirak Patra
• 金额: $ 19.03万
• 依托单位: University College London
• 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%2FZ532952%2F1
• 关键词: Molecular; strategy; developing; instant; nanomedicine

CONTEXT: There exists a pressing clinical need in the UK and globally to make strategy for generating therapeutics within or in close proximity to clinical facilities for timely delivery to patients, i.e., point-of-care (POC) manufacturing. This concept encompasses the production of drugs, vaccines, cell, and nucleic acid therapies (e.g., gene therapies, mRNA vaccines, nanomedicines, etc.) for the treatment of a diverse array of diseases, ranging from rare conditions to more prevalent ones such as cancer, infections, severe burns, or diabetes.The UK Medicines and Healthcare products Regulatory Agency (MHRA) has recently brought forth a new regulatory framework specifically designed for the in-hospital POC manufacturing of therapies. This initiative will alleviate the existing challenges of using therapeutics with a limited shelf-life and supply-chain issues such as low-temperature storage (e.g., mRNA nanovaccines) and will expand the range and availability of new innovative therapies in the NHS.CHALLENGES THE PROJECT ADDRESSES: Nanomedicine despite its initial successes and effectiveness with products like Doxil®, Abraxane®, Marqibo®, Stimuvax®, etc., it has not fully realized its potential. Challenges such as manufacturing complexity, formulation intricacies, upscaling difficulties, low solubility, colloidal stability loss during storage, limited shelf-life, and stringent storage conditions (e.g., -80 °C), as encountered with COVID-19 vaccines using solid-lipid nano formulations (e.g., Pfizer/BioNTech and Moderna), are contributory factors that limit its full impact.Therefore, a simpler manufacturing and formulation strategy together with long-term stability for storage are unmet crucial needs. We propose to develop an innovative molecular platform for a point-of-care instant nano formulation (inFORM) to address the principal bottleneck of manufacturing therapeutics on-site.AIMS & OBJECTIVES: The focused aims of this project are to:WP1(1-9months) Rationally design a molecular strategy to develop a self-assembled peptide for making instant drug formulation: We will develop a rationally designed peptide library for self-assembly and capable of simple and quick drug encapsulation for point-of-care (POC) manufacturing.WP2(9-18months): Screening encapsulation efficiency for selected FDA approved drugs and nucleic acids with different chemical structure to build inFORM library: The inFORM library will be optimised for instant co-acervation, packaging and self-assembling to an easy formulation by manipulating the co-acervation and self-assembly process by simple methods such as by mixing, small change in pH, ionic strength, heat, redox potential, sonication, vortexing etc for simple and quick drug formulation.The proposed inFORM project is perfectly aligned with this EPSRC call 'to address key bottlenecks in future medicines manufacturing pipeline'. The inFORM proposals will serve the purpose of this call 'through speculative, high-risk ideas that could potentially offer high reward'.POTENTIAL IMPACT: The inFORM approach will address one of the principal bottleneck issues of existing nanomedicine and point-of-care instant manufacturing. A library of peptide nanoarchitectures will be developed for coacervation and instant packaging of drugs and nucleic acids. Designing and employing such coacervating peptides to serve as a specific nano formulation with the proposed strategy has never been developed and tested. Therefore, this innovative approach can generate significant step-change results for future study, IPs, and can have significant impacts on future steps in nanomedicine and point-of care therapy both clinically and commercially. The success of inFORM will have a significant impact on modular manufacture (e.g., hospital, GP, OPD, pharmacies), mobile manufacture, POC manufacture and potentially home-based manufacture to fulfil the UK mission.

背景：在英国和全球范围内存在迫切的临床需求，以制定在临床设施内或附近产生治疗剂的策略，以及时递送给患者，即，点护理（POC）制造。这一概念包括药物、疫苗、细胞和核酸疗法（例如，基因疗法、mRNA疫苗、纳米医学等）用于治疗各种疾病，从罕见疾病到更常见的疾病，如癌症、感染、严重烧伤或糖尿病。英国药品和保健产品监管局（MHRA）最近提出了一个新的监管框架，专门针对医院内POC治疗产品的生产。这一举措将缓解使用具有有限保质期和供应链问题（如低温储存（例如，mRNA纳米疫苗），并将扩大范围和新的创新疗法在NHS的可用性。挑战项目地址：纳米医学尽管其初步的成功和有效性与产品，如Doxil®，Abraxane®，Marqibo®，Stimuvax®等，它尚未充分发挥其潜力。挑战如制造复杂性、配方复杂性、放大困难、低溶解度、储存期间胶体稳定性损失、有限的保质期和严格的储存条件（例如，-80 °C），如使用固体-脂质纳米制剂的COVID-19疫苗所遇到的（例如，辉瑞/BioNTech和Moderna）是限制其全面影响的促成因素。因此，更简单的生产和配方策略以及长期储存稳定性是尚未满足的关键需求。我们建议开发一个创新的分子平台，用于即时纳米制剂（inFORM），以解决现场制造治疗剂的主要瓶颈。目标和关键：该项目的重点目标是：WP 1（1- 9个月）合理设计分子策略，开发自组装肽，用于制备即时药物制剂：我们将开发一个合理设计的肽库，用于自组装，并能够简单快速地包封药物，用于护理点（POC）制造。（9- 18个月）：筛选FDA批准的药物和具有不同化学结构的核酸的包封效率，以构建inFORM文库：inFORM库将针对即时凝聚、包装和自组装进行优化，以通过简单方法操纵凝聚和自组装过程，例如通过混合、pH值、离子强度、加热、氧化还原电位的微小变化、超声处理，所提出的inFORM项目与EPSRC的呼吁“解决未来药品生产线的关键瓶颈”完全一致。inFORM提案将服务于这一呼吁的目的“通过投机，高风险的想法，可能提供高回报”。潜在影响：inFORM方法将解决现有的纳米医学和即时护理制造的主要瓶颈问题之一。肽纳米结构库将被开发用于药物和核酸的凝聚和即时包装。设计和使用这种凝聚肽作为具有所提出的策略的特定纳米制剂从未被开发和测试过。因此，这种创新的方法可以为未来的研究，IP产生显着的阶跃变化结果，并可能对临床和商业上的纳米医学和即时治疗的未来步骤产生显着影响。inFORM的成功将对模块化制造产生重大影响（例如，医院、全科医生、门诊部、药房）、移动的制造商、POC制造商和潜在的家庭制造商，以履行英国的使命。