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，非侵入性的仓库监控工具，可以提供有关注入仓库状态的真实的时间的关键信息。这种低成本的装置将在临床前研究和临床环境中应用，用于长效储库开发，以加速这一过程。我们设想，该设备可以开发，以造福患者，包括不同的肤色，在家里作为一种评估和监测储药性能，使个性化的储药剂量和管理时间表在未来的方式。我们的项目地址，并及时的背景下，目前在制药工业中对治疗药物库作为能够实现长期递送的药物的兴趣迅速增加，用于治疗包括癌症、HIV、神经系统疾病和精神病在内的疾病的经典小分子药物和生物制剂。长效贮库的目的是在数周或数月的时间内控制患者治疗;它消除了重复每日注射的必要性，解决了诸如血浆和组织药物水平变化或长期患者治疗不依从性等问题。需要长效注射技术的开发中药物比例增加，特别是生物制剂，进一步推动了需求。目前，任何药物的长效可注射贮库在其口服制剂批准后需要约10年的开发。这是由于需要了解贮库在注射部位组织内的行为，以及对治疗药物的释放和生物利用度的相关影响。因此，开发针对个体患者具有保证体内特定释放特性的长效制剂是极其困难的。此外，在药物开发或患者治疗期间的临床前研究中，还没有实时监测其性能的方法。我们的目标是开发基于光声原理的低成本、非侵入性可注射储库表征工具的概念，该工具可以提供关于储库特性和体内局部组织反应的信息。目标是：为了定义规范并构建原型光声仪器，以形成能够测量仓库行为关键参数的低成本设备的基础。制造和优化原型光声仪器数据采集所需的长效贮库制剂。在“模型”生物条件下使用（i）建立的体外组织模拟模型和（ii）在临床前，体内注射到皮下大鼠组织中。内部和广泛使用的代码实时监测注射贮库的关键参数将提供了解贮库行为所需的监测信息，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，以收集这些信息在一个安全的，非侵入性的方式最初临床前，随后设想其在临床试验和治疗中的使用。这是一种新颖而务实的解决问题的方法，为低成本实施提供了一条强有力的途径。