Transdermal delivery of macromolecules mediated by microneedle arrays

微针阵列介导的大分子透皮递送

• 批准号: BB/E020534/1
• 负责人: Ryan Donnelly
• 金额: $ 43.17万
• 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: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FE020534%2F1
• 关键词: Transdermal; delivery; macromolecules; mediated; microneedle

Traditional pharmaceutical drugs are small chemical molecules that treat the symptoms of a disease. Biopharmaceuticals are large biological molecules, known as peptides and proteins and these target the underlying mechanisms and pathways of a disease. They can deal with targets in humans that are not accessible with traditional medicines. Recently, there have been rapid and revolutionary developments in this field of biotechnology. Therapeutic peptides and proteins are expected to be used extensively in coming years as vaccines and treatments for cancer, high blood pressure, pain and blood clots, as well as many other illnesses. However, one of the major challenges to successful clinical use of these 'biotech' molecules is their efficient delivery to the site of action. The body breaks these drugs 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 causes pain and means that such drugs are usually only given to people in hospital. If these new drugs could be delivered across the skin, then many of the problems associated with their administration could be overcome. However, in order to do this, it is necessary to overcome the barrier presented by the outer layer of the skin. This skin layer, known as the stratum corneum, has evolved to protect us from the external environment. It prevents entry of dirt and microorganisms, but also most medicines. In this project, a novel type of transdermal patch will be developed that will by-pass the stratum corneum barrier. On its surface will be many tiny needles that pierce the stratum corneum without causing any pain - the sensation is said to feel like a cat's tongue or sharkskin. These needles will either dissolve quickly, leaving tiny holes in the stratum corneum, which will let proteins and peptides enter the body, or swell, turning into a jelly-like material that keeps the holes open and will allow continuous drug delivery. The technology developed here is unique and could potentially revolutionise delivery of peptides and proteins. This is likely to be of great benefit to patients, as it will make these advanced medicines readily available to everybody.

传统药物是治疗疾病症状的小化学分子。生物制药是大型生物分子，称为肽和蛋白质，它们针对疾病的潜在机制和途径。它们可以处理传统药物无法达到的人体目标。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在未来几年广泛用作癌症、高血压、疼痛和血栓以及许多其他疾病的疫苗和治疗方法。然而，成功临床使用这些“生物技术”分子的主要挑战之一是它们如何有效地传递到作用位点。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，这会引起疼痛，并且意味着此类药物通常只提供给住院患者。如果这些新药可以通过皮肤输送，那么许多与给药相关的问题就可以得到解决。然而，为了做到这一点，必须克服皮肤外层所呈现的屏障。这种皮肤层被称为角质层，它的进化是为了保护我们免受外部环境的影响。它可以防止污垢和微生物以及大多数药物的进入。在该项目中，将开发一种新型的透皮贴剂，该贴剂将绕过角质层屏障。它的表面会有许多细小的针，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或鲨鱼皮一样。这些针要么会快速溶解，在角质层上留下小孔，让蛋白质和肽进入体内，要么会膨胀，变成果冻状材料，使孔保持打开状态，从而实现持续的药物输送。这里开发的技术是独一无二的，有可能彻底改变肽和蛋白质的输送。这可能会给患者带来很大好处，因为它将使每个人都能轻松获得这些先进药物。

项目成果

Microneedle-mediated vaccine delivery: harnessing cutaneous immunobiology to improve efficacy.

微针介导的疫苗递送：利用皮肤免疫生物学来提高功效。

• DOI: http://dx.10.1517/17425247.2012.676038
• 发表时间: 2012
• 期刊: Expert opinion on drug delivery
• 作者: Al

Vaccine delivery systems.

疫苗输送系统。

• DOI: http://dx.10.1080/21645515.2016.1259043
• 发表时间: 2017
• 期刊: Human vaccines & immunotherapeutics
• 影响因子: 4.8
• 作者: Donnelly RF

Hydrogel-Forming Microneedle Arrays for Enhanced Transdermal Drug Delivery.

用于增强透皮药物输送的水凝胶形成微针阵列。

• DOI: http://dx.10.1002/adfm.201200864
• 发表时间: 2012
• 期刊: Advanced functional materials
• 影响因子: 19
• 作者: Donnelly RF

Hydrogel-forming microneedles prepared from "super swelling" polymers combined with lyophilised wafers for transdermal drug delivery.

由“超膨胀”聚合物与冻干晶圆结合制成的水凝胶形成微针，用于透皮药物输送。

• DOI: http://dx.10.1371/journal.pone.0111547
• 发表时间: 2014
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Donnelly RF

How can microneedles overcome challenges facing transdermal drug delivery?

微针如何克服透皮给药面临的挑战？

• DOI: http://dx.10.4155/tde-2017-0028
• 发表时间: 2017
• 期刊: Therapeutic delivery
• 影响因子: 4.2
• 作者: Donnelly RF