How does a University change the World?

Developing the Prototype for the Nicotine Patch

 

The prevalence of smoking is one of the biggest public health threats facing the world. It is estimated that nearly six million people die every year from tobacco related illnesses and up to half of current smokers will eventually die of a tobacco-related illness. Research shows that eight out of ten smokers want to quit, and that four out of every ten smokers try to quit each year, however, addiction to nicotine can be very difficult to overcome with some studies reporting that only 35% manage to quit on their first attempt.

Today, there are a wide variety of smoking cessation approaches, books, and products available to help smokers quit but in the 1980s, a now common smoking cessation system, nicotine replacement therapy, was in its infancy. In early 1984 a research partnership between two Trinity College Dublin scientists and Irish pharmaceutical company, Elan Corporation led the team to develop the world's first commercial nicotine patch. It was subsequently patented around the world in 1990, a development which has contributed to countless numbers of people quitting smoking and an unquantifiable benefit to human population health and reduced mortality.

The project began when a former Trinity Professor of Medical Genetics who was then Chief Executive of the Irish pharmaceutical company Elan Corporation approached Professor of Pharmaceutics, Owen Corrigan and Professor of Physical Chemistry John Corish in Trinity and asked them if they could design and make an electrically-driven drug delivery system, also known as iontophoretic delivery, which could deliver active pharmaceutical compounds across the skin.

Professor Corrigan’s range of expertise included drug delivery system design and pharmacokinetics, which is the science of the rate of uptake and subsequent working life of a drug in the body. Professor Corish’s research interests lay in the study of the passive and electrically driven atomic-scale transport of matter through solid materials. Their combined expertise made them the perfect match to investigate this drug delivery innovation.
As the research progressed, Elan focussed their request on nicotine and the creation of a method for the treatment of withdrawal symptoms associated with smoking cessation. It would take the form of an electrically driven delivery system which would deliver nicotine to the individual, through their skin. This would act as a nicotine replacement system for the smoker - giving them pure nicotine to ease the physiological urge to smoke without the harmful elements contained in tobacco products. Professors Corish and Corrigan brought in a PhD student Yvonne Bannon to work with them on the project.

By the 1980s there was considerable scientific evidence regarding smoking as a form of drug dependence. Nicotine is delivered into a smoker’s bloodstream in an initial burst when they smoke a cigarette but the nicotine level rapidly declines. The urge to smoke increases as the nicotine level continues to fall below a given level in the blood, which varies with each smoker. The objective for any smoking cessation therapy involving nicotine administration would be the rapid attainment and maintenance of a certain level of nicotine in the blood.
At the time, a number of approaches were being used in smoking cessation therapy including nicotine gum. The scientists found a number of challenges with the existing gum which their new invention would need to overcome, for example, the need to take the gum frequently in order to keep nicotine levels up and the inability to use the gum during sleep which would mean that the individual would have very low levels of nicotine in the morning and would have a return of the urge to smoke. Another issue with the need for frequent use of the gum was the potential psychological reinforcement of the habit of frequent smoking.
The scientists faced the challenge then of producing a product which could deliver nicotine through the skin using only a single daily application that could reproduce the levels of nicotine observed in habitual smokers and would be able to decrease or eradicate nicotine dependence and break the smoking habit.

The initial request from Elan was for a patch which would be electrically driven. However, while comparing an electrically driven versus passive system, using bespoke made glassware for the initial tests rather than humans or animals, Professors Corish and Corrigan actually discovered a way to move the nicotine into skin cells without the use of an electric current.
When they believed they understood the system sufficiently well to design a patch that could deliver the nicotine to the required level they made prototype patches and decided to test these on themselves. With a plan to test their saliva samples for analysis for nicotine content at regular intervals during the day, they applied the patches and went about their usual day’s work. Occasional cigar and pipe smoker Professor Corish noticed a slight nicotine type buzz while Professor Corrigan, a never smoker, felt unwell from the delivery of nicotine into his blood and had to remove the patch. In the end, Professor Corish’s experience of using nicotine in the lab and realising what a toxic substance nicotine is caused him to decide to give up smoking altogether.

With this initial success achieved, the process moved forward to clinical trials in Elan in Athlone with volunteers. A quit-rate study showed that for each week of the study the percentage of volunteers in the nicotine patch group who abstained from smoking was almost twice that in the placebo group.

Professors Corish and Corrigan’s work resulted in several US patents being sought and achieved for a patch which allowed nicotine to move from the patch, through the skin into the bloodstream at a constant rate which could over time be reduced through smaller, or lower dose patches. The product was licensed in over 20 countries and many thousands of smokers are likely to have benefited from the help these patches have given them to quit smoking.

Cancer is a strategic research theme in Trinity, with a programme which involves research across a number of areas including basic science, translation medicine, health economics and planning, and global health. For more information about the ongoing research on cancer in Trinity please click here: http://www.tcd.ie/research/themes/cancer/