Project 3: Ionic liquids and eutectic solvents
Project Overview:
In the third, and youngest, of the GSK-EML projects a multidisciplinary team of doctors, scientists and engineers are conducting collaborative research to provide more effective drug delivery. They hope to do so by harnessing the potential of ionic liquids and deep eutectic solvents for use as Active Pharmaceutical Ingredients (APIs) or formulation additives. Ionic liquids and deep eutectic solvents possess unexpected and remarkable properties such as increased chemical stability, increased permeability and increased solubility in comparison to their respective parent molecules.
Research on the synthesis and characterisation of ILs and DESs is being undertaken to help determine their pharmacokinetic and tissue distribution properties and interactions with model cellular membranes. By discovering if ILs and DESs mimic known biochemical intra- and inter-cellular mechanisms, the team can determine if these can be incorporated into APIs and/or excipients in pharmaceutical formulations to optimize properties such as permeability and receptor recognition.
A key aim will be to provide a suite of generic predictive models that can make a major contribution to our understanding and the accurate representation of the thermodynamic behaviour and transport properties of pharmaceutically-relevant ILs/DESs. This includes developing a targeted understanding of small molecule and specific functional group interactions that underpin macroscopic behaviours.
Meet the team
The Aboagye Group
The Aboagye Group is involved in the development of probes for molecular imaging of cancer together with investigation of pre-clinical and clinical pharmacology of novel therapeutics. Radiochemistry and pharmacokinetic/mathematical modelling are integral to the programme.
Professor
Faculty of Medicine, Department of Surgery & Cancer
The Hunt Group
The Hunt Group has led in the computational study and understanding of ILs and DES, we specifically focus on developing a fundamental chemical understanding which allows us to establish direct connections between the molecular level and macroscopic properties. We address questions such as; How do the molecules of an IL interact with each other, with a solute? If the IL is functionalised what effect will this have on the local interactions and on the macroscopic properties such as viscosity, solubility or chemical reactivity? Which quantum level information is necessary input for a macroscopic model, and which information can be ignored or subsumed into a general parameter? Providing such parameters based on high level quantum chemical calculations.
Reader in Computational and Theoretical Chemistry
Faculty of Natural Sciences, Department of Chemistry
The Molecular Systems Engineering Group
The Molecular Systems Engineering Group has led the development of a group-contribution molecular-based equation of state, SAFT-γ, that makes it possible to predict multiphase multicomponent phase behaviour of complex mixtures (e.g., electrolytes and hydrogen bonding fluids). The group has demonstrated how this approach can be used to accelerate coarse-grained simulations of aggregation and transport phenomena and to enable computer-aided molecular design.
Participating members:
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Professor of Chemical Engineering |
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Professor of Chemical Physics |
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Prof. Amparo Galindo |
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Please note that only those academics from the MSEG listed above are affiliated with the GSK-EML project |
The Membrane Biophysics Platform (MBP)
The Membrane Biophysics Platform (MBP) is a leading centre in the development and application of technologies for manufacturing and characterising biological membranes including their interactions with small molecules and proteins. Using these systems the MBP is able to fabricate biomembranes that closely mimic translocation pathways in-vivoand use these platforms to establish engineering rules that correlate efficacy and membrane transport with small molecule structure.
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Reader in Chemical Biology & Membrane Biophysics |
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Research Lecturer |
The Welton Group
The Welton Group has led the academic effort to understand the links between the physicochemical and solvent properties of ionic liquids, their interactions with solute species and the effects of these on the chemical reactivies of these solutes.
Dean of the Faculty of Natural Sciences
Faculty of Natural Sciences
Lisa McQueen
GSK's Lisa McQueen has expertise in the solid state chemistry and properties of small molecule APIs. She is leading the emergence of the application of API ionic liquids to drug development and drug delivery at GSK. Collaborative resources from GSK may include formulation development and drug delivery science, analytical spectroscopy, DMPK and specific therapeutic area biology.
Lisa McQueen
Senior Scientific Investigator,
GSK
Project motivation
The pharmaceutical industry is undergoing a critical change driven by significantly lower return rates on research investment from the disappearance of blockbuster assets and the threat of generic competition. In an enterprising and innovative response to this change, GSK is influencing and adopting drug delivery technologies early in the drug discovery pathway.
Currently drug delivery is treated as a solution to discovery development challenges and the hope is that the change of tact, which this project is exploring, will create value for patients by reducing side effects, providing new treatment options and enabling patent friendly routes of delivery.
Perhaps most importantly, however, this project is motivated by the preliminary research produced by GSK, which first showed the untapped qualities of Ionic Liquids and Deep Eutectic Solvents. They are tapping into the expertise within this area at Imperial to further explore the possibilities.