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.

传统的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，被称为多肽和蛋白质，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靶点。近年来，在这一生物技术领域有了迅速而革命性的发展。治疗性多肽和蛋白质预计将在未来几年广泛用于疫苗和癌症、高血压、疼痛和血栓以及许多其他疾病的治疗。然而，这些“生物技术”分子在临床成功使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，身体会分解这些药物，它们通常不能很好地吸收到血液中。因此，它们必须经常通过注射的方式给药，这会引起疼痛，这意味着这些药物通常只给住院的人服用。如果这些新药可以通过皮肤传递，那么许多与给药有关的问题就可以被克服。然而，为了做到这一点，有必要克服皮肤外层的屏障。这层皮肤，被称为角质层，已经进化到保护我们免受外部环境的伤害。它可以防止灰尘和微生物进入，也可以防止大多数药物进入。在这个项目中，将开发一种新型的透皮贴片，可以绕过角质层屏障。在它的表面会有许多微小的针头刺入角质层而不会引起任何疼痛——据说这种感觉就像猫的舌头或鲨鱼的皮肤。这些针头要么会迅速溶解，在角质层留下小孔，让蛋白质和肽进入体内，要么会膨胀，变成一种果冻状的物质，使这些小孔保持开放，从而允许持续的药物输送。这里开发的技术是独一无二的，可能会彻底改变肽和蛋白质的输送方式。这可能对病人有很大的好处，因为它将使这些先进的药物随时可供每个人使用。

项目成果

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

Design, optimization and characterisation of polymeric microneedle arrays prepared by a novel laser-based micromoulding technique.

• DOI: 10.1007/s11095-010-0169-8
• 发表时间: 2011-01
• 期刊: PHARMACEUTICAL RESEARCH
• 影响因子: 3.7
• 作者: Donnelly, Ryan F.;Majithiya, Rita;Singh, Thakur Raghu Raj;Morrow, Desmond I. J.;Garland, Martin J.;Demir, Yusuf K.;Migalska, Katarzyna;Ryan, Elizabeth;Gillen, David;Scott, Christopher J.;Woolfson, A. David
• 通讯作者: Woolfson, A. David

Microneedle arrays allow lower microbial penetration than hypodermic needles in vitro.

• DOI: 10.1007/s11095-009-9967-2
• 发表时间: 2009-11
• 期刊: PHARMACEUTICAL RESEARCH
• 影响因子: 3.7
• 作者: Donnelly, Ryan F.;Singh, Thakur Raghu Raj;Tunney, Michael M.;Morrow, Desmond I. J.;McCarron, Paul A.;O'Mahony, Conor;Woolfson, A. David
• 通讯作者: Woolfson, A. David

Hydrogel-Forming Microneedle Arrays for Enhanced Transdermal Drug Delivery.

• DOI: 10.1002/adfm.201200864
• 发表时间: 2012-12-05
• 期刊: ADVANCED FUNCTIONAL MATERIALS
• 影响因子: 19
• 作者: Donnelly, Ryan F.;Singh, Thakur Raghu Raj;Garland, Martin J.;Migalska, Katarzyna;Majithiya, Rita;McCrudden, Cian M.;Kole, Prashant Laxman;Mahmood, Tuan Mazlelaa Tuan;McCarthy, Helen O.;Woolfson, A. David
• 通讯作者: Woolfson, A. David

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

• DOI: 10.1517/17425247.2012.676038
• 发表时间: 2012-05
• 期刊: Expert opinion on drug delivery
• 影响因子: 6.6
• 作者: Al-Zahrani S;Zaric M;McCrudden C;Scott C;Kissenpfennig A;Donnelly RF
• 通讯作者: Donnelly RF