Micron-scale, chemically-controlled, auto-injection systems for at-home drug delivery

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、蛋白质和抗体，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、蛋白质和抗体预计将在未来几年广泛用于疫苗和癌症、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。COVID-19大流行大大增加了在远离医疗机构的家中自行注射的需求，在医疗机构中，传播可能产生可怕的后果，医疗系统积压。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。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。这些针在角质层上制造出微小的孔，药物/疫苗可以从一个独特的由简单而安全的化学反应驱动的储存系统进入体内。我们独特的技术可能会彻底改变肽和蛋白质、抗体、疫苗以及目前无法通过皮肤传递的长效小分子的传递。在英国，国家医疗服务体系（NHS）从家庭给药/疫苗中获益，而这通常需要医护人员的时间和专业知识。最终，有能力的病人将通过改善疾病控制来提高与健康有关的生活质量。在家治疗，使人们远离医疗机构，还将有助于减少COVID-19和其他呼吸道病原体（如流感、甲型链球菌）向脆弱的住院患者和卫生保健工作者的传播，同时重要的是，使NHS工作人员能够专注于克服非COVID-19疾病正常诊断和治疗方面的积压。我们已经吸引了工业界相当大的兴趣和资金来开发我们的第一代和第二代微针技术，用于一系列应用。然而，为了促进第三代新技术的转化发展，并最大限度地提高英国的价值，有必要开发方法来充分了解这些新的高剂量微针。我们会采用先进的电脑引导装置设计和合理化，并进行广泛的实验室调查，以确保这些装置的功效。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, proteins and antibodies, 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, proteins and antibodies are expected to be used extensively in the coming years 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 and healthcare systems are backlogged. 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. 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 create tiny holes in the stratum corneum, through which drugs/vaccines can enter the body from a unique reservoir system powered by simple and safe chemistry. Our unique technology could potentially revolutionise the delivery of peptides and proteins, antibodies, vaccines, as well as that of long-acting small molecules that cannot currently be delivered across the skin. In the UK, the NHS stands to benefit from at-home dosing of medicines/vaccines that normally require a healthcare worker's time and expertise. Ultimately, health-related-quality-of-life will be enhanced through improved disease control by empowered patients. At-home treatment, keeping people away from healthcare settings, will also help reduce spread of COVID-19 and other respiratory pathogens (e.g. influenza, Strep A) to vulnerable in-patients and healthcare workers whilst also, importantly, allowing NHS staff to focus on overcoming the backlog in normal diagnosis and treatment of non-COVID disease.We have attracted considerable interest and funding from industry to develop our first and second generation microneedle technologies for a range of applications. However, to facilitate the translational development of the novel third generation technology to be investigated here and maximise value to the UK, it is essential to develop methods to fully understand these new high-dose microneedles. We will ensure that their efficacy is guaranteed by employing advanced computer-guided device design and rationalisation, coupled with extensive laboratory investigation. Ultimately, commercialisation of the technology will be the primary route by which UK industry, the NHS and patients will derive benefits.