Transdermal delivery of macromolecules mediated by microneedle arrays

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.

Advances in biotechnology have allowed the economical and large-scale production of therapeutically important peptides and proteins. One of the major challenges to successful clinical use of these 'biotech' molecules is their efficient delivery to the site of action. Due to enzymatic breakdown and poor absorption, parenteral delivery is presently the most routinely-employed method for administering macromolecular agents. Transdermal delivery offers one potential means of overcoming many of the problems associated with delivery of these drugs. Microneedle arrays are minimally invasive devices that can by-pass the stratum corneum barrier to drug diffusion. Such microneedle arrays are applied to the skin surface and painlessly pierce the epidermis, creating microscopic holes through which drugs diffuse. In this project, it is intended to develop a unique transdermal drug delivery system based on microneedle arrays. Following thorough physicochemical characterisation of candidate materials and microneedle geometries, the device will be produced and used to deliver model macromolecules across the skin.