Microneedle-mediated enhanced Raman therapeutic drug monitoring

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Over the past 3 decades there has been a dramatic increase in the number of people infected with human immunodeficiency virus and Mycobacterium tuberculosis, such that approximately 40 million are currently infected by HIV and 14 million are infected with tuberculosis. Strict compliance with prescribed drug treatment regimens is required for management of these diseases in individuals and control of their spread to others. Monitoring of compliance using conventional methods is problematic, particularly in the Developing World, where lack of resources and improper use of needles causes significant problems for society. Advances in medical treatment mean more premature neonates now survive. Due to their prematurity and the associated complications, these patients are frequently treated with multiple drugs. Direct blood sampling can, however, cause severe bruising or scarring and such patients also have very limited blood volumes, which prevents frequent sampling. One in five fatal car accidents in the UK are currently due to drivers driving under the use of illegal or prescription drugs. No appropriate roadside test currently exists. When considering these factors, in addition to the time-consuming nature and expense of routine therapeutic drug monitoring in hospitals, it is obvious that development of novel non- or minimally-invasive technologies that permit rapid and frequent ambulatory monitoring without drawing of blood is extremely important. In this project, we will investigate novel technology based on tiny needles that puncture the outer layer of skin without causing any pain or bleeding - the sensation is said to feel like a cat's tongue or sharkskin. These needles will then swell, turning into a jelly-like material that keeps the holes open and allow collection of skin fluid. As the drug content in the fluid in people's skin is very similar to that in their blood, we can use our microneedles, in combination with a sophisticated measurement technique, known as Surface-enhanced Raman Spectroscopy, to accurately monitor blood levels of drugs.Once developed, the technology described here will allow frequent routine monitoring of patients. Accordingly, drug- and exogenous substance-associated adverse events and complications arising from blood sampling will be prevented, to the benefit of patients Worldwide. In the UK, the NHS will benefit from reduced costs due to shorter hospital stays and reduced occurrence of inappropriate dosing. Ultimately, health-related-quality-of-life will be enhanced through improved disease control, rapid detection of dangerously high or low levels, facile monitoring of adherence to prescribed regimens (eg treatment of tuberculosis in the Developing World) and detection of illicit substances in addicts or vehicle drivers. Preterm neonates are likely to derive great benefit from the marked increase in monitoring frequency permitted, as are elderly patients being treated with multiple drugs. Ultimately, commercialisation of the technology will be the primary route by which UK industry, the NHS and patients will derive benefits. In order to attract potential industrial partners, it is vitally important to demonstrate proof of concept for this technology, which is the over-arching aim of the present proposal.