Microneedle-mediated enhanced Raman therapeutic drug monitoring

在过去30年中，感染人类免疫缺陷病毒和结核分枝杆菌的人数急剧增加，目前约有4 000万人感染艾滋病毒，1 400万人感染结核病。严格遵守规定的药物治疗方案是管理这些疾病的个人和控制其传播给他人所必需的。使用常规方法监测遵守情况是有问题的，特别是在发展中国家，那里缺乏资源和不适当使用针头给社会造成重大问题。医学治疗的进步意味着现在有更多的早产儿存活下来。由于早产和相关并发症，这些患者经常接受多种药物治疗。然而，直接采血可能导致严重的瘀伤或疤痕，并且此类患者的血量也非常有限，这妨碍了频繁的采血。目前，英国五分之一的致命车祸是由于司机使用非法或处方药驾驶。目前没有适当的路边测试。当考虑这些因素时，除了医院中常规治疗药物监测的耗时性质和费用之外，很明显，开发允许快速和频繁的动态监测而无需抽血的新型非侵入性或微创技术是极其重要的。在这个项目中，我们将研究基于微小针头的新技术，这些针头刺穿皮肤外层而不会引起任何疼痛或出血-据说感觉就像猫的舌头或鲨鱼皮。这些针会膨胀，变成一种类似于海绵的材料，使孔保持开放，并允许收集皮肤液体。由于人体皮肤内液体中的药物含量与血液中的药物含量非常相似，我们可以使用我们的微针，结合称为表面增强拉曼光谱的复杂测量技术，精确监测血液中的药物含量。一旦开发出来，这里描述的技术将允许对患者进行频繁的常规监测。因此，将预防药物和外源性物质相关的不良事件和血液采样引起的并发症，使全球患者受益。在英国，由于住院时间缩短和剂量不当的发生率降低，NHS将受益于成本降低。最终，通过改进疾病控制、快速检测危险的高或低水平、方便地监测对规定方案的遵守情况（如发展中国家的肺结核治疗）以及检测吸毒者或车辆驾驶员体内的非法物质，将提高与健康有关的生活质量。早产儿可能会从允许的监测频率的显著增加中获益匪浅，接受多种药物治疗的老年患者也是如此。最终，该技术的商业化将是英国工业、NHS和患者从中受益的主要途径。为了吸引潜在的工业合作伙伴，展示这项技术的概念证明至关重要，这是本提案的首要目标。

Over the past 3 decades there has been a dramatic increase in the number of people infected with human immunodeficiency virus and Mycobacterium tuberculosis, such that approximately 40 million are currently infected by HIV and 14 million are infected with tuberculosis. Strict compliance with prescribed drug treatment regimens is required for management of these diseases in individuals and control of their spread to others. Monitoring of compliance using conventional methods is problematic, particularly in the Developing World, where lack of resources and improper use of needles causes significant problems for society. Advances in medical treatment mean more premature neonates now survive. Due to their prematurity and the associated complications, these patients are frequently treated with multiple drugs. Direct blood sampling can, however, cause severe bruising or scarring and such patients also have very limited blood volumes, which prevents frequent sampling. One in five fatal car accidents in the UK are currently due to drivers driving under the use of illegal or prescription drugs. No appropriate roadside test currently exists. When considering these factors, in addition to the time-consuming nature and expense of routine therapeutic drug monitoring in hospitals, it is obvious that development of novel non- or minimally-invasive technologies that permit rapid and frequent ambulatory monitoring without drawing of blood is extremely important. In this project, we will investigate novel technology based on tiny needles that puncture the outer layer of skin without causing any pain or bleeding - the sensation is said to feel like a cat's tongue or sharkskin. These needles will then swell, turning into a jelly-like material that keeps the holes open and allow collection of skin fluid. As the drug content in the fluid in people's skin is very similar to that in their blood, we can use our microneedles, in combination with a sophisticated measurement technique, known as Surface-enhanced Raman Spectroscopy, to accurately monitor blood levels of drugs.Once developed, the technology described here will allow frequent routine monitoring of patients. Accordingly, drug- and exogenous substance-associated adverse events and complications arising from blood sampling will be prevented, to the benefit of patients Worldwide. In the UK, the NHS will benefit from reduced costs due to shorter hospital stays and reduced occurrence of inappropriate dosing. Ultimately, health-related-quality-of-life will be enhanced through improved disease control, rapid detection of dangerously high or low levels, facile monitoring of adherence to prescribed regimens (eg treatment of tuberculosis in the Developing World) and detection of illicit substances in addicts or vehicle drivers. Preterm neonates are likely to derive great benefit from the marked increase in monitoring frequency permitted, as are elderly patients being treated with multiple drugs. Ultimately, commercialisation of the technology will be the primary route by which UK industry, the NHS and patients will derive benefits. In order to attract potential industrial partners, it is vitally important to demonstrate proof of concept for this technology, which is the over-arching aim of the present proposal.