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。生物制药是较大的分子，例如肽和蛋白质，它们针对传统药物无法触及的疾病的潜在机制和途径。近年来，生物技术这一领域取得了快速且革命性的发展。治疗性肽和蛋白质预计将越来越多地用作疫苗以及癌症、高血压、疼痛、血栓和许多其他疾病的治疗方法。然而，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递送到作用位点。当这些药物被吞咽时，身体会分解它们，并且它们通常不能很好地吸收到血液中。因此，必须经常通过注射给药，这很痛苦，并且意味着这些药物通常只能在医院施用。长效小分子制剂在治疗艾滋病毒和结核病方面日益受到关注，也必须进行注射。 COVID-19 大流行大大增加了在家中自行注射注射剂的需求，远离医疗机构，因为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污染的锐器的困难都导致迫切需要注射药物/疫苗的替代输送方式。同样，开发无血诊断系统是一个主要优先事项。我们开发了一种新型透皮贴剂，可以绕过皮肤的屏障层（称为角质层）。贴片表面有许多细小的针，可以刺穿角质层，但不会引起任何疼痛——据说这种感觉就像猫的舌头一样。这些针要么快速溶解，在角质层留下小孔，药物可以通过这些孔进入体内，要么膨胀，变成果冻状材料，使孔保持打开状态并允许持续的药物输送。我们独特的技术可能会彻底改变肽和蛋白质的输送，以及目前无法穿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，而无需实际采集血液样本。在英国，由于住院时间缩短和不适当剂量的发生减少，国民医疗服务体系 (NHS) 将从成本降低中受益。最终，通过改善疾病控制、快速检测疾病和危险的高或低药物含量、轻松监测处方剂量的遵守情况以及检测吸毒者或车辆驾驶员中的非法物质，将提高与健康相关的生活质量。早产儿将受益于监测频率的显着增加，接受多种药物治疗的老年患者也将受益匪浅。在家治疗/诊断，让人们远离医疗机构，也将有助于减少 COVID-19 在弱势住院患者和医护人员中的传播。我们吸引了业界的极大兴趣和资金来研究我们的技术的一系列应用。然而，为了促进商业化进程并最大限度地为英国带来价值，现在有必要开发合理化微针皮肤应用的方法，以便每次都以相同的方式将它们应用于每位患者，并保证其功效。我们还将首次在行业标准条件下研究重复使用我们的微针以模拟正常使用并证明安全性。最终，该技术的商业化将成为英国工业界、NHS 和患​​者受益的主要途径

项目成果

Solid implantable devices for sustained drug delivery.

用于持续药物输送的固体植入装置。

• DOI: 10.1016/j.addr.2023.114950
• 发表时间: 2023-06-07
• 期刊: Advanced drug delivery reviews
• 影响因子: 16.1
• 作者: Elizabeth R Magill;S. Demartis;E. Gavini;A. Permana;R. Thakur;M. Adrianto;David Waite;Katie Glover
• 通讯作者: Katie Glover