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种低成本、非侵入性的药库监控工具，可以实时提供有关注射药库状态的关键信息。这种低成本设备将应用于临床前研究和临床环境中的长效储库开发，以加速这一进程。我们设想，开发该设备可以使患者受益，包括不同肤色的患者，在家中作为评估和监测储库性能的一种方式，从而实现未来储库剂量和给药时间表的个性化。我们的项目解决了这一问题，并且是及时的目前，制药行业对治疗药物长效药物的兴趣迅速增加，因为这些药物能够长期输送经典小分子药物和生物制剂，用于治疗癌症、艾滋病毒、神经系统疾病和精神病等疾病。长效制剂的目的是在数周或数月的时间内控制患者的治疗；它消除了每天重复注射的必要性，解决了血浆和组织药物水平变化或长期患者治疗不合规等问题。开发中需要长效注射技术的药物（尤其是生物制品）比例的增加进一步推动了需求。目前，任何药物的长效注射长效制剂在其口服制剂获得批准后都需要约 10 年的开发时间。这是因为需要了解储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，开发具有保证个体患者体内特定释放曲线的长效储库是极其困难的。此外，在药物开发或患者治疗期间的临床前研究中，没有方法可以实时监测它们的表现。我们的目标是开发一种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，可以提供有关仓库特征和体内局部组织反应的信息。目标是：定义规范并构建原型光声仪器，该仪器将构成能够测量仓库关键参数的低成本设备的基础原型光声仪器采集数据所需的长效制剂的设计、制造和优化。这将包括选择储库组成成分和药物，以及选择适当的光声造影剂。使用（i）建立的体外组织模拟模型和（ii）在“模型”生物条件下采集光声信号临床前、体内注射到大鼠皮下组织中。使用内部和广泛使用的代码对来自储库的光声信号进行建模实时监控注射储库的关键参数将提供了解储库行为并帮助预测药物释放及其生物利用度所需的监测信息。我们建议最初在临床前使用光声监测和测量以安全、非侵入性的方式收集这些信息，然后设想将其用于临床试验和治疗。这是解决该问题的一种新颖而务实的方法，为低成本实施提供了强有力的途径。