Non invasive methods to accelerate the development of injectable therapeutic depots

非侵入性方法加速注射治疗储库的开发

• 批准号: EP/Z532976/1
• 负责人: Maria Marlow
• 金额: $ 19.06万
• 依托单位: University of Nottingham
• 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%2FZ532976%2F1
• 关键词: Non; invasive; methods; accelerate; development

Our vision is to create a low-cost, non-invasive depot monitoring tool that can provide key information about the state of an injected depot in real time. This low-cost device will have applications in preclinical studies and in the clinical setting for long-acting depot development to accelerate the process. We envisage that the device could be developed to benefit patients, including different skin tones, at home as a way of assessing and monitoring depot performance, enabling personalisation of the depot dose and the administration schedule in the future.Our project addresses, and is timely in the context of, the current rapid increase in interest in therapeutic drug depots within the pharmaceutical industry as medicines capable of achieving long term delivery of classical small-molecule drugs and biologics for the treatment of diseases including, cancer, HIV, neurological disease and psychoses. A long-acting depot aims to control patient therapy over a period of weeks or months; it eliminates the necessity for repeated daily injections addressing issues such as variation in plasma and tissue drug levels or non-compliance in long term patient therapy. Demand is further driven by the increased proportion of drugs in development requiring long-acting injectable technologies, particularly biologicals. Currently, introduction to the market of a long-acting injectable depot of any drug takes ~10 years of development after approval of its oral formulation. This is due to the requirement to understand the depot's behaviour within the injection site tissue, and linked effects on release, and bioavailability of the drug for therapy. Consequently, it is extremely difficult to develop long-acting depots with a guaranteed specific release profile in-vivo for individual patients. Moreover, there is no method for real-time monitoring of their performance in preclinical studies during medicine development or during patient therapy.Our goal is to develop the concept of a low-cost, non-invasive injectable depot characterisation tool based on photoacoustic principles that can provide information on depot characteristics and in-vivo local tissue response.Objectives are:To define the specification and build prototype photoacoustic instrumentation that would form the basis of a low-cost device capable of measuring key parameters of the depot's behaviourDesign, fabrication and optimisation of a long-acting depot formulation required for data acquisition by the prototype photoacoustic instrumentation. This will include selection of depot constituent components and a drug, as well as a selection of appropriate photoacoustic contrast agents.Acquisition of photoacoustic signal in 'model' biological conditions using (i) established in-vitro tissue-mimicking phantoms and (ii) in preclinical, in-vivo injection into subcutaneous rat tissue.To model photoacoustic signals from the depot using in-house and widely available codeMonitoring key parameters of injected depot in real-time will provide surveillance information required to understand the depot's behaviour and aid in prediction of drug release and its bioavailability. We propose the use of photoacoustic monitoring and measurement to gather this information in a safe, non-invasive manner initially preclinically and subsequently envisage its use in clinical trials and therapy. This is a novel and pragmatic approach to the problem with a strong pathway to a low-cost implementation.

我们的愿景是创建一个低成本的非侵入性仓库监控工具，该工具可以实时提供有关注射仓库状态的关键信息。这种低成本设备将在临床前研究和临床环境中进行长效仓库开发的应用，以加速该过程。我们设想，可以开发该设备以使患者受益，包括不同的肤色，以评估和监视仓库性能，实现将来的仓库剂量和管理时间表的个性化，并在未来的情况下进行。包括癌症，艾滋病毒，神经系统疾病和精神病在内的疾病。长效仓库旨在在数周或几个月内控制患者治疗；它消除了每天重复注射的必要性，以解决等问题等问题，例如血浆和组织药物水平的变化或长期患者治疗中的不合规性。需求进一步推动了需要长效注射技术（尤其是生物学家）的开发药物的比例增加。目前，在批准其口服表述后，对任何药物的长效注射库的市场介绍都需要大约10年的开发。这是由于需要了解注射部位组织中仓库的行为以及对释放的影响以及药物治疗的生物利用度的联系。因此，为个别患者开发具有保证的特定释放概况的长效库是极其困难的。 Moreover, there is no method for real-time monitoring of their performance in preclinical studies during medicine development or during patient therapy.Our goal is to develop the concept of a low-cost, non-invasive injectable depot characterisation tool based on photoacoustic principles that can provide information on depot characteristics and in-vivo local tissue response.Objectives are:To define the specification and build prototype photoacoustic instrumentation that would form the basis of a low-cost device capable of测量仓库行为设计的关键参数，制造和优化由原型光声仪器进行数据采集所需的长效仓库公式。这将包括选择仓库成分和药物的选择，以及选择适当的光声对比剂。在“模型”生物条件下，使用（i）使用（i）使用（i）使用（i）使用（i）使用（i）在抗蛋白链抗细节，无线电图中的图片脉冲构图示意图中的幻象和（ii）的光声信号。注射仓库的密钥参数实时将提供了解库的行为所需的监视信息，并有助于预测药物释放及其生物利用度。我们建议使用光声监测和测量以安全的，非侵入性的方式收集此信息，最初是临床上的，随后设想其在临床试验和治疗中的使用。这是解决问题的一种新颖而务实的方法，具有强大的低成本实施途径。