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。生物药物是更大的分子，例如多肽和蛋白质，它们针对的是疾病的潜在机制和途径，而传统药物无法获得这些机制和途径。近年来，这一生物技术领域取得了突飞猛进的革命性发展。预计治疗性多肽和蛋白质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。然而，这些所谓的“生物技术”分子在临床上成功应用的主要挑战之一是有效地将它们输送到作用部位。当这些药物被吞噬时，人体会分解它们，它们通常不会被血液很好地吸收。因此，他们不得不频繁地通过注射给药，这是痛苦的，也意味着这些药物通常只在医院使用。还必须注射在治疗艾滋病毒和结核病方面日益突出的长效小分子制剂。新冠肺炎的流行极大地增加了在家中、远离医疗机构自我管理注射剂的需求，在医疗机构中传播可能会产生可怕的后果。储存、分配和管理的复杂性、针头恐惧症以及国内处置可能受到污染的利器的困难，都导致迫切需要替代注射药物/疫苗的输送方式。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，它绕过了皮肤的屏障层，称为角质层。贴片表面有许多微小的针头，穿透角质层而不会引起任何疼痛--据说这种感觉就像猫的舌头。这些针头要么迅速溶解，在角质层留下微小的孔，药物可以通过角质层进入人体；要么膨胀，变成一种胶状物质，保持孔的开放，并允许持续的药物输送。我们独特的技术可能会给肽和蛋白质的输送带来革命性的变化，以及目前无法通过皮肤输送的长效小分子的输送。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和疾病标志物的水平，而不需要实际采集血液样本。在英国，由于住院时间缩短和不适当剂量的发生减少，NHS将受益于成本的降低。归根结底，与健康有关的生活质量将通过改进疾病控制、快速检测疾病和危险的高水平或低水平药物、方便地监测规定剂量的遵守情况以及检测吸毒者或车辆司机的非法物质而得到提高。早产儿将从允许的监测频率显著增加中获得巨大好处，接受多种药物治疗的老年患者也将受益。家庭治疗/诊断使人们远离医疗保健环境，这也将有助于减少新冠肺炎向脆弱的住院患者和医护人员的传播。我们吸引了来自行业的相当大的兴趣和资金，以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最大限度地增加英国的价值，现在有必要开发合理的微针皮肤应用方法，使它们每次都以相同的方式应用于每个患者，并确保其疗效。我们还将首次在行业标准条件下研究重复应用我们的微针，以模拟正常使用并证明安全。最终，这项技术的商业化将是英国工业界、英国国民健康保险制度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