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：在英国和全球存在着紧迫的临床需求，以制定策略，以在临床设施内或与临床设施附近生成治疗，以及时向患者（即服务点（POC）制造）及时提供治疗。这个概念包括药物，疫苗，细胞和核酸疗法的产生（例如，基因疗法，mRNA疫苗，纳米医学等），以治疗各种疾病的潜水疾病，范围从罕见的疾病，从罕见的疾病到更为普遍的疾病，例如癌症，癌症，严重的烧伤和糖尿病。专为院底POC疗法制造而设计的监管框架。该举措将减轻使用治疗的现有挑战，其保质期和供应链问题，例如低温储存（例如mRNA纳米诺伐），并将扩大NH的新创新疗法的范围和可用性。 Stimuvax®等。它尚未完全意识到其潜力。诸如制造复杂性，制定复杂性，升级困难，低可溶性，储存过程中的胶体稳定性损失，保质期有限和严格的存储条件（例如-80°C）（例如，使用covid-19疫苗使用固体固体 - 纳米纳米式造成的效果（例如，pfizer/bodere inter Its in limimitiont in limimition），诸如covid-19疫苗遇到的挑战（例如-80°C）。因此，更简单的制造和公式策略以及长期储存的稳定性是未满足的至关重要的需求。 We propose to develop an innovative molecular platform for a point-of-care instant nano formula (inFORM) to address the principal bottleneck of manufacturing therapy on-site.AIMS & OBJECTIVES: The focused aims of this project are to:WP1(1-9 months) Rationally design a molecular strategy to develop a self-assembled peptide for making instant drug formula: We will develop a rationally designed peptide library for self-assembly WP2（9-18个月），能够简单而快速的药物封装（POC）制造：筛选封装效率的封装效率，具有不同化学结构的FDA批准的药物和具有不同化学结构的核酸来构建信息图书馆：通过对即时的共同保护，包装和自动化的方式进行简化的方法，以进行信息库进行优化，并通过操作和自动进行自动进行操作，并进行自动启动，并进行自动启动，并进行自动启动，并进行自动搜索，并进行自动化的方法，并进行自动化的方法，并进行自动化的方法，并进行自动化，并进行自动化，并进行自动化，并进行自动化的方法，并进行自动化的方法，并进行自动化的方式，并进行自动化的方法，并进行自动化的方法，并进行自动化的方法，并进行自动化的方法，并进行自动化的方法，并进行自动启动。 pH，离子强度，热量，氧化还原潜力，超声处理，涡旋等，用于简单，快速的药物配方。拟议的信息项目与此EPSRC呼叫完全一致，以“解决未来药品制造管道中的关键瓶颈”。信息建议将通过“投机性高风险想法”来实现此呼吁的目的，这些想法有可能提供高度的奖励。将开发一个肽纳米结构的库，用于过度的药物和核酸的即时包装。从未开发和测试使用和采用这种过度的肽作为特定的纳米形成，以作为特定的纳米形成。因此，这种创新的方法可以为IPS，IPS产生重大的逐步变化结果，并可以在临床和商业上对纳米医学和医疗点疗法的未来步骤产生重大影响。 Inform的成功将对模块化制造（例如医院，GP，OPD，药房），移动制造，POC制造和潜在基于家庭的制造业产生重大影响，以实现英国任务。