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The treatment and prevention of disease to maintain health and well-being is both an important part of our life and society, with new pharmaceuticals and remedies needed for the ever increasing diversity of illnesses and disease, many of which are increasingly challenging to treat with current medicines. Less than 10% of the world’s biodiversity has been examined for their utilisation in pharmaceuticals and significant progress is not being made in doing so. This is because natural product (NP) screening has largely been replaced by combinatorial chemistry and high throughput synthesis as the major route for pharmaceutical development. This strategy is clearly failing, with few new successful drug candidates being patented, with many major pharmaceutical companies downsizing and closing as a result. A new successful pharma discovery route is desperately needed. Coupled with this is the lack of robust, safe and realistic process options and technology being used at the earliest stage of NP screening, making scaling up to NP production processes to commercial scale both problematic and unreliable. This common outcome is caused by the ingrained practice of not involving Chemical Engineers at the earliest product development stages, resulting in processes and technologies constrained by fixed chemistry and bench-scale process analogues.
To overcome these issues, which are holding back NP product development, new solvent-resistant membranes will be developed and fabricated (and compared to commercially available alternatives) using techniques developed within the Patterson Research group at the University of Bath (UK) and University of Auckland (New Zealand).
The variables that will be investigated to optimise the NP extraction include: solvent type, temperature, pH, extraction time, agitation and effect of innovative enhancements such as ultrasonic agitation and microwave heating. Dead-end cell membrane testing will be used to quickly establish the efficacy of different membranes, solvents, and filtration temperatures and pressures. For separations with rejections greater than 90%, optimisation will be conducted in cross-flow cells, investigating long term performance. In this way, new combinations of solvents and membranes will, for the first time, be applied to fractionate these NPs, including greener solvents such as vegetable oils, enhanced by nanofiltration. The active species will be identified by a range of techniques, including HPLC, GC-MS, LC-MS, FTIR-ATR and XRD. In parallel with this, Imperial College will trial extractions and membrane separations as above, but will establish the beneficial properties of the isolates (e.g. testing for antioxidant, anti-inflammatory and antibacterial properties).
Initial benchmarking, modelling and testing of the equipment and membrane extraction techniques will be conducted initially using well characterised NPs, such as olives, where the analytical techniques for the active compounds (here polyphenols such as hydroxytyrosol) have already been established in my research group. Thereafter, the project will become very innovative, as we develop and optimise fractionations and identify active species and test them for beneficial properties, as above, for NPs where only limited work exists.
Success in this project would bring Chemical Engineers and Chemical Engineering to the forefront of this important and developing area of NP derived medicines.
Funding Notes:
This will cover the home rate University tuition fees for up to three years with a stipend of £13,600 (tax free) in the first year with an increase in years 2 and 3. This is available for students with British citizenship, UK Settled status, or who are ‘ordinarily resident’ in the UK for three years prior to grant start. Otherwise, only University tuition fees can be covered for EU citizens. Candidates should be expecting, or already holding, a first class or upper second class degree in Chemical Engineering, Chemistry or a related subject.