Optimisation of microneedle insertion and understanding the implications of repeat application as tools to support translation

传统药物是治疗疾病症状的小分子药物。生物制药是大分子，例如多肽和蛋白质，其目标是传统药物无法获得的疾病的潜在机制和途径。近年来，在这一生物技术领域有了迅速而革命性的发展。治疗性多肽和蛋白质预计将越来越多地被用作疫苗以及癌症、高血压、疼痛、血栓和许多其他疾病的治疗方法。然而，这些所谓的“生物技术”分子在临床成功应用的主要挑战之一是它们能否有效地递送到作用部位。当这些药物被吞下时，身体会分解它们，它们通常不能很好地吸收到血液中。因此，他们必须经常通过注射给药，这是痛苦的，这意味着这些药物通常只在医院使用。小分子长效制剂在治疗艾滋病毒和结核病方面日益领先，也必须注射。2019冠状病毒病大流行大大增加了在远离医疗保健机构的家中自我注射的需求，在医疗保健机构中，传播可能产生可怕的后果。储存、分发和管理的复杂性、针头恐惧症以及国内处置可能受到污染的尖锐物的困难，都促使迫切需要可注射药物/疫苗的替代递送方式。同样，开发无血诊断系统也是一个主要优先事项。我们开发了一种新型的透皮贴片，可以绕过皮肤的屏障层，也就是角质层。贴片表面有许多微小的针头，这些针头可以刺穿角质层而不会引起任何疼痛——据说这种感觉就像猫的舌头一样。这些针头要么迅速溶解，在角质层留下小洞，药物可以通过这些小洞进入体内，要么膨胀成果冻状物质，使这些洞保持开放，使药物持续输送。我们独特的技术可能会彻底改变肽和蛋白质的输送，以及目前无法通过皮肤输送的长效小分子。值得注意的是，我们还发现我们的可膨胀微针可以从皮肤中提取液体。这使我们能够监测药物水平和疾病标志物，而无需实际采集血液样本。在英国，由于住院时间缩短，减少了不适当剂量的发生，NHS将从降低的成本中受益。最终，将通过改进疾病控制、迅速发现疾病和危险的高或低剂量药物、方便地监测遵守规定剂量的情况以及在成瘾者或车辆驾驶员身上发现非法物质，提高与健康有关的生活质量。早产儿将从允许的监测频率的显著增加中获益良多，接受多种药物治疗的老年患者也是如此。在家治疗/诊断，使人们远离医疗机构，也将有助于减少COVID-19向弱势住院患者和医护人员的传播。我们已经吸引了工业界的大量兴趣和资金来研究我们的技术在一系列应用中的应用。然而，为了促进商业化进程并使英国的价值最大化，现在必须开发合理的微针皮肤应用方法，以便每次都以相同的方式应用于每位患者，并保证其功效。我们还将首次在行业标准条件下研究我们的微针的重复应用，以模拟正常使用并证明安全性。最终，这项技术的商业化将是英国工业、NHS和患者受益的主要途径

Traditional pharmaceutical drugs are small molecules that treat the symptoms of a disease. Biopharmaceuticals are larger molecules, for example, peptides and proteins, which target the underlying mechanisms and pathways of a disease that are not accessible with traditional drugs. Recently, there have been rapid and revolutionary developments in this field of biotechnology. Therapeutic peptides and proteins are expected to be used increasingly as vaccines and as treatments for cancer, high blood pressure, pain, blood clots and many other illnesses. However, one of the major challenges to successful clinical use of these so-called "biotech" molecules is their efficient delivery to the site of action. The body breaks these medicines down when they are swallowed and they are generally not well-absorbed into the blood. As a result, they have to be given frequently by injection, which is painful and means that these drugs are usually only administered in hospital. Long-acting formulations of small molecules, increasingly to the fore in treating HIV and TB, must also be injected. The COVID-19 pandemic has greatly increased the need for self-administration of injectables at home, away from healthcare settings, where transmission can have dire consequences. Complexities of storage, distribution and administration, needle phobia and the difficulty of domestic disposal of potentially-contaminated sharps all contribute to an urgent need for alternative delivery modes for injectable drugs/vaccines. Similarly, development of blood-free diagnostic systems is a major priority. We have developed a novel type of transdermal patch that by-passes the skin's barrier layer, which is called the stratum corneum. The patch surface has many tiny needles that pierce the stratum corneum without causing any pain - The sensation is said to feel like a cat's tongue. These needles either dissolve quickly, leaving tiny holes in the stratum corneum, through which medicines can enter the body, or swell, turning into a jelly-like material that keeps the holes open and allows continuous drug delivery. Our unique technology could potentially revolutionise the delivery of peptides and proteins, as well as that of long-acting small molecules that cannot currently be delivered across the skin. Notably, we have also found that our swellable microneedles can extract fluid from the skin. This permits us to monitor the levels of medicines and markers of disease without actually taking blood samples. In the UK, the NHS stands to 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 disease and dangerously high or low levels of medicines, facile monitoring of compliance with prescribed dosing and detection of illicit substances in addicts or vehicle drivers. Preterm neonates will derive great benefit from the marked increase in monitoring frequency permitted, as will elderly patients being treated with multiple medicines. At-home treatment/diagnosis, keeping people away from healthcare settings, will also help reduce spread of COVID-19 to vulnerable in-patients and healthcare workers.We have attracted considerable interest and funding from industry to investigate our technologies for a range of applications. However, to facilitate the commercialisation process and maximise value to the UK, it is now essential to develop methods for rationalised skin application of the microneedles such that they are always applied to every patient in the same way every time and that their efficacy is guaranteed. We will also study, for the first time under industry-standard conditions, repeat application of our microneedles to mimic normal use and to demonstrate safety. Ultimately, commercialisation of the technology will be the primary route by which UK industry, the NHS and patients will derive benefits