Towards digital health: Real-time monitoring and personalisation of immunosuppressive therapies using 3D printing

全世界每年进行93，000例器官移植，患者终身接受免疫抑制治疗。这些狭窄的治疗指数药物需要定期监测和剂量滴定，这是一个非常昂贵和耗时的过程，每年花费NHS超过1.36亿英镑。为了减轻医疗服务的负担并改善患者的治疗效果，需要一种新的监测和药物给药方法。因此，该项目旨在设计一个非侵入性平台，用于实时免疫抑制监测和使用三维打印（3DP）的个性化给药。该项目将分为两个部分：第1部分）开发一种便携式设备，用于使用表面增强拉曼光谱（Sers）快速评估非侵入性生物液体（例如唾液）中的药物水平;第2部分）基于Sers设备的临床反馈开发包含治疗剂的个性化3D打印剂型。通过这两种尖端技术的交叉，免疫抑制的管理将在未来发生革命性变化，降低医疗成本并预防严重药物毒性的风险。该项目解决了EPSRC的关键主题（特别是开发未来疗法的重大挑战），重点是监测和个性化治疗的创新工程。在该项目中，该平台将被开发并应用于免疫抑制方案，短期内将在体外和离体模型中进行评估，以证明概念验证。此外，Sers和3DP技术的杂交可应用于监测其他疾病领域的窄治疗指数药物。

Around the world, 93,000 organ transplants are performed annually, with patients being maintained on lifelong immunosuppressive therapy. These narrow therapeutic index drugs require regular monitoring and dose titrations, a process which is highly expensive and time-consuming, costing the NHS over £136 million annually. To reduce the burden on healthcare services and improve patient outcomes, a new method of monitoring and drug dosing is required. As such, this project aims to engineer a non-invasive platform for real-time immunosuppressive monitoring and personalised dosing using three-dimensional printing (3DP). The project will be split into two parts: Part 1) development of a portable device for the rapid evaluation of drug levels in non-invasive biological fluids (e.g. saliva) using surface enhanced Raman spectroscopy (SERS), and; Part 2) Development of personalised 3D printed dosage forms containing therapeutic agent based on the clinical feedback from the SERS device. Via the intersection of these two cutting edge technologies, the management of immunosuppression will in the future be revolutionised, reducing healthcare costs and preventing the risk of severe drug toxicities. This project addresses key themes of the EPSRC (especially Developing Future Therapies grand challenge) with a focus on innovative engineering for the monitoring and personalisation of treatments. Within this project, the platform will be developed and applied to immunosuppressive regimes, which in the short term would be evaluated in in vitro and ex-vivo models to demonstrate proof-of-concept. In addition, the hybridisation of SERS and 3DP technologies could be applied to monitor narrow therapeutic index drugs in other disease areas.