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

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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.