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

优化微针插入并了解重复应用作为支持翻译工具的影响

• 批准号: EP/V047221/1
• 负责人: Ryan Donnelly
• 金额: $ 158.03万
• 依托单位: Queen's University Belfast
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FV047221%2F1
• 关键词: Optimisation; microneedle; insertion; understanding; implications

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

传统药物是治疗疾病症状的小分子。生物药物是较大的分子，例如肽和蛋白质，它们针对传统药物无法获得的疾病的潜在机制和途径。最近，在这一生物技术领域，已经有了迅速而革命性的发展。预计治疗性肽和蛋白质将越来越多地用作疫苗和癌症治疗，高血压，疼痛，血凝块和许多其他疾病。但是，成功临床使用这些所谓的“生物技术”分子的主要挑战之一是它们有效地递送到行动部位。当这些药物吞咽时，身体会破坏这些药物，并且通常不会充分吸收血液。结果，必须经常通过注射给予它们，这很痛苦，这意味着这些药物通常仅在医院服用。还必须注射小分子的长效制剂，越来越多地治疗艾滋病毒和结核病。 COVID-19大流行极大地增加了对家里注射剂的自我管理的需求，远离医疗保健环境，在这种情况下，传播可能会带来可怕的后果。储存，分配和给药的复杂性，针恐惧症以及国内处置潜在污染尖锐的困难都有助于迫切需要对可注射药物/疫苗的替代输送模式。同样，无血液诊断系统的发展是重点。我们开发了一种新型的透皮贴片，该贴片绕过皮肤的屏障层，这称为角质层。斑块表面有许多微小的针，可以刺穿角膜层而不会引起任何疼痛 - 据说感觉就像是猫的舌头。这些针要么迅速溶解，在角膜层中留下微小的孔，药物可以进入身体，要么膨胀，变成一种类似果冻的材料，可保持孔的打开状态并允许连续药物输送。我们独特的技术可能会彻底改变肽和蛋白质的输送，以及目前无法跨皮肤递送的长效小分子的递送。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。这使我们可以在不实际服用血液样本的情况下监测疾病的药物和标志物的水平。在英国，NHS将受益于由于住院时间较短和不适当剂量的发生降低而受益匪浅。最终，通过改善疾病控制，疾病的快速检测以及危险的高或低水平药物，可轻松监测对处方药的剂量的依从性，并在成瘾者或车辆驾驶员中对非法物质的检测，可以通过改善疾病的快速检测以及危险的高或低水平的药物来增强生活质量的生活。早产新生儿将从允许的监测频率的明显增加中获得巨大的好处，而老年患者接受了多种药物治疗。在家的治疗/诊断，使人们远离医疗保健环境，还将有助于减少199日与脆弱的住院患者和医护人员的传播。我们吸引了行业的大量兴趣和资金来调查我们的一系列应用技术。但是，为了促进商业化过程并最大程度地提高英国的价值，现在必须开发合理的皮肤应用方法，以便每次以相同的方式将它们应用于每个患者，并保证其功效。我们还将在行业标准的条件下首次研究，重复使用微乳腺癌来模仿正常使用并证明安全性。最终，该技术的商业化将是英国行业，NHS和患者将获得福利的主要途径