The most effective drug treatments for lung disease are delivered via aerosol inhalation, but the details of how pharmaceutical aerosols behave in the humid environment of the lung, and trigger a biological response, need to be better understood so that dosage, side effects and other factors can be controlled.
Dr Allen Haddrell, a Research Assistant in the School of Chemistry, realised that studying drug delivery to the lung required a multidisciplinary approach, drawing on expertise in physical chemistry, aerosol science and microbiology. A central question for the project is how an aerosol’s hygroscopic qualities – that is, its capacity for attracting and holding water molecules – affects total and regional dose in the lung during inhalation.
‘The benefits of a pharmaceutical drug can be greatly improved by targeting the dose to the region of injury,’ explains Dr Haddrell. ‘In the case of diseases of the lung, this means the delivery of the drug on an aerosol droplet to specific regions in the lung. This is challenging because of the lung’s complex structure and highly humid environment. If we can reverse-engineer aerosols that target specific regions within the lung, this should enable the overall dose of the drug to be reduced, resulting in a more cost-effective treatment that also limits side-effects.’
An Elizabeth Blackwell Institute Early Career Fellowship, funded by the Wellcome Trust, enabled Dr Haddrell to explore the behaviour of aerosol droplets during inhalation, then use this understanding to design starting formulations to deliver the dose most effectively to specific regions in the lung. His research is based in the Bristol Aerosol Research Centre, a newly established laboratory facility with a focus on atmospheric science and industrial applications of aerosols.
Dr Haddrell used a technique he developed during his PhD to generate particles of particular chemical composition and size and dose them directly onto the surface of a lung cell culture. The advantage of this technique is that it directly mimics the cell-aerosol interaction observed in the human lung. He conducted this work in collaboration with Dr Lea Ann Dailey at the Institute of Pharmaceutical Science, King’s College, London.
In the course of the project, Dr Haddrell and his colleagues measured the hygroscopic behaviour of numerous FDA-approved chemicals (such as citric acid), modelled their subsequent deposition pattern within the lung, and established a strong causal relationship between the addition of specific chemicals and where, and how much of, the dose is delivered in the lung.
The project’s second stage laid the groundwork for designing a new aerosol deposition device. This infrastructure has been completed and installed in the Bristol Aerosol Research Centre, and although Dr Haddrell’s Fellowship has come to an end, the work continues – work that would not have been possible without his EBI Early Career Fellowship.
Dr Haddrell’s work on pharmaceutical aerosols continues. A developing collaboration with the Southampton Respiratory Biomedical Research Unit will use advanced lung imaging techniques to map deposition patterns directly in human subjects.