Engineering a topical hypobaric patch: A needle-free solution for biopharmaceutical drug administration into the skin

设计局部低压贴片：用于将生物制药药物注入皮肤的无针解决方案

• 批准号: EP/S021167/1
• 负责人: Stuart Jones
• 金额: $ 58.9万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FS021167%2F1
• 关键词: Engineering; topical; hypobaric; patch; needle

Scientific advances in the last 3 decades have resulted in the development and use of medicines that act to correct very specific malfunctions in the human body. However, the active component of these newer medicines is now typically much larger than those used in medicines in the past. For example, 20 years ago a common example of an active ingredient in a medicine was aspirin, with a molecular mass of 180 Da. In comparison, newer medicines which are commonly used today, for example, insulins and hormones have a molecular mass of aprox. 10,000 Da, i.e. they are 100 times larger, and the most complex agents e.g., monoclonal antibodies, are in the range of 145,000- 160,000 Da, i.e., 1000 times larger. The high molecular mass of these new active ingredients in medicines, often termed, biopharmaceutical actives or advanced therapies, has created medicine manufacture, quality control and administration challenges, which together make it difficult to develop this new type of medicines.One of the most problematic issues in developing medicines containing biopharmaceutical actives in humans is that they cannot be administered as a simple tablet. Their complexity means that they are easily degraded if they are simply swallowed with a glass of water and their size means that they find it difficult to pass into the body. As a consequence most biopharmaceutical agents are injected. Using needles to inject medicines has a number drawbacks including, but not limited to, needle stick injuries, patients not wanting to take the medicine, needle phobia and disease transmission, particularly when the needles are re-used and used incorrectly. In response to these issues scientists have been developing a number of 'needle-free' medical devices that have the potential to deliver the newest types of medicines to patients in their own homes.In this project a device, which has been shown capable of delivering biopharmaceutic actives into the skin without the use of needles in the laboratory, will developed to the point that it can be used in the clinical setting with patients. The device uses a small chamber (the size of a ten pence piece) to apply topical hypobaric pressure, which generates a parabolic deformation of the skin that thins the tissue, opens the hair follicles and increases the skin blood flow underneath the chamber. The hypobaric chamber self-seals onto the skin and it will remain airtight during a 30 min application protocol, which is painless and when it is removed the skin is not damaged. This needle-free approach to delivery has the advantages that it does not break the skin, it can deliver both charged and neutral molecules effectively. The delivery process is controlled over a 30 min period and hence active penetration depth into the skin is consistent.To facilitate the device development the project will systematically investigate how hypobaric pressure modifies the properties of the skin and how these changes subsequently alter drug delivery. It will develop a mathematical model to describe the delivery of large active agents from medicines into the skin and use this mathematical model to guide the fabrication hypobaric device that can be used by patients. It will test and develop the device both in-vitro and in-vivo and it will generate proof-of-concept data with a novel active for skin regeneration provided by a commercial partner.

过去30年的科学进步导致了药物的开发和使用，这些药物可以纠正人体中非常具体的功能障碍。然而，这些新药的活性成分现在通常比过去药物中使用的活性成分大得多。例如，20年前，药物中活性成分的常见例子是阿司匹林，分子量为180 Da。相比之下，今天常用的较新药物，例如胰岛素和激素的分子量约为180 Da。10，000 Da，即它们大100倍，并且最复杂的试剂，例如，单克隆抗体的分子量在145，000 - 160，000 Da的范围内，即，大一千倍。药物中这些新活性成分的高分子量，通常被称为生物药物活性物质或先进疗法，已经产生了药物制造、质量控制和给药挑战，这些挑战一起使得开发这种新型药物变得困难。在开发含有人体生物药物活性物质的药物中最棘手的问题之一是它们不能作为简单的片剂给药。它们的复杂性意味着，如果它们只是用一杯水吞下，它们很容易降解，它们的大小意味着它们很难进入体内。因此，大多数生物药剂被注射。使用针来注射药物具有许多缺点，包括但不限于针刺伤、患者不想服药、针恐惧症和疾病传播，特别是当针被重复使用和不正确使用时。为了解决这些问题，科学家们一直在开发一些“无针”医疗设备，这些设备有可能在患者自己的家中将最新类型的药物输送给患者。在该项目中，一种设备已经被证明能够在实验室中不使用针头将生物药剂活性物质输送到皮肤中，该设备将被开发到可以在临床环境中用于患者的程度。该装置使用一个小腔室（10便士硬币大小）来施加局部低压，这会使皮肤产生抛物线变形，从而使组织变薄，打开毛囊并增加腔室下方的皮肤血流。低压舱自动密封在皮肤上，在30分钟的应用程序中保持气密，这是无痛的，当它被移除时，皮肤不会受损。这种无针递送方法的优点是它不会破坏皮肤，它可以有效地递送带电和中性分子。输送过程控制在30分钟内，因此进入皮肤的有效渗透深度是一致的。为了促进设备的开发，该项目将系统地研究低压如何改变皮肤的特性，以及这些变化如何随后改变药物输送。它将开发一个数学模型来描述从药物到皮肤的大活性剂的输送，并使用这个数学模型来指导制造可供患者使用的低压设备。它将在体外和体内测试和开发该设备，并将使用商业合作伙伴提供的新型皮肤再生活性物质生成概念验证数据。

项目成果

In-Silico Modelling of Transdermal Delivery of Macromolecule Drugs Assisted by a Skin Stretching Hypobaric Device.

• DOI: 10.1007/s11095-022-03423-7
• 发表时间: 2023-01
• 期刊: PHARMACEUTICAL RESEARCH
• 影响因子: 3.7
• 作者: Sebastia-Saez, Daniel;Benaouda, Faiza;Lim, Chui Hua;Lian, Guoping;Jones, Stuart A.;Cui, Liang;Chen, Tao
• 通讯作者: Chen, Tao

Needleless administration of advanced therapies into the skin via the appendages using a hypobaric patch.

• DOI: 10.1073/pnas.2120340119
• 发表时间: 2022-05-03
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Benaouda, Faiza;Inacio, Ricardo;Lim, Chui Hua;Park, Haeeun;Pitcher, Thomas;Alhnan, Mohamed A.;Aly, Mazen M. S.;Al-Jamal, Khuloud;Chan, Ka-lung;Gala, Rikhav P.;Sebastia-Saez, Daniel;Cui, Liang;Chen, Tao;Keeble, Julie;Jones, Stuart A.
• 通讯作者: Jones, Stuart A.

Numerical analysis of the strain distribution in skin domes formed upon the application of hypobaric pressure

施加低压时形成的皮肤圆顶应变分布的数值分析

• DOI: 10.48550/arxiv.2010.13849
• 发表时间: 2020
• 作者: Sebastia-Saez D

A Cyclodextrin-Stabilized Spermine-Tagged Drug Triplex that Targets Theophylline to the Lungs Selectively in Respiratory Emergency.

• DOI: 10.1002/adtp.202000153
• 发表时间: 2020-12
• 期刊: Advanced therapeutics
• 影响因子: 4.6
• 作者: Sofian ZM;Benaouda F;Wang JT;Lu Y;Barlow DJ;Royall PG;Farag DB;Rahman KM;Al-Jamal KT;Forbes B;Jones SA
• 通讯作者: Jones SA