Grŵp Therapïau Uwch
The Advanced Therapies Group, within the School of Dentistry, is involved in using our knowledge of the molecular and cellular control of human disease processes to inform the design, development and testing of novel polymer therapeutics in the prevention and treatment of difficult to treat, often life-threatening infections. The work of the group is focused on polymer therapies derived from nature in applied research, and their use in a range of applications in the prevention and treatment of human disease.
A significant area of our research is employed in investigating a low molecular weight alginate (OligoG CF-5/20), which has been shown to enhance the activity of conventional antibiotics against multi-drug resistant Gram-negative bacteria and biofilms, for example, Pseudomonas and Burkholderia spp. which complicate the treatment of cystic fibrosis. This work is now being broadened to tailor the alginate to its maximum potential therapeutic effect. The group is also characterising microbial growth on novel nanocellulose wound dressing materials for chronic wound applications.
Key achievements have been in developing new strategies to specifically target otherwise undeliverable proteins, peptides and drugs to sites of disease by the chemical bonding of safe, water-soluble natural polymers extracted from plants and animals. These so-called "nanomedicines" are capable of reducing the side effects of conventional drugs by 'enveloping' them in a polymer 'coat', so that once they reach the site of disease, they can be triggered to release the drug by the body's own proteins. Thus, patients require lower doses and less frequent dosing.
- AlgiPharma AS, Sandvika, Norway
- SINTEF Materials and Chemistry, Trondheim, Norway
- Norwegian University of Science and Technology (NTNU), Trondheim, Norway
- Paper and Fibre Research Institute (PFI), Trondheim, Norway
- Respiratory Diagnostics Group, College of Medicine, Swansea University
- Centre for Nanohealth, College of Medicine, Swansea University
Research here, as part of a multi-national collaboration with AlgiPharma AS, has involved development of polymer therapies based on the biopolymer alginate, derived from seaweed. The first product, currently in Phase IIb clinical trials is OligoG, a low molecular weight alginate oligosaccharide. We first demonstrated in 2010 how these oligomeric structures were able to potentiate antibiotics (by up to 500-fold) against a range of multi-drug resistant (MDR) human pathogens and inhibit biofilm formation. Subsequent research sponsored by the EU, US Department of Defence, Cystic Fibrosis Foundation and the EU Eurostars Programme has led to the optimisation of the delivery of OligoG as an inhalation therapy for cystic fibrosis and in the treatment of patients with life-threatening infections of MDR bacteria, where work is ongoing in the group.
The Advanced Therapies Group are a key part of a four year £5.4 million research grant from the Norwegian Research Council in collaboration with AlgiPharma AS, SINTEF and NTNU, Norway looking into the development of novel alginate oligomers for clinical use. This exciting programme is a vital component of an International consortium to investigate microbial sources of raw material for the formulation of new prevention strategies and treatments for persistent, difficult to treat infections for AlgiPharma's alginate technology programme.
This project is involved in the development of bio-compatible cellulose nanomaterials (derived from tree pulp) with innovative, functional properties for advanced wound healing applications in conjunction with the Paper Research Institute (PFI), Trondheim. The ability of these nanofibres (from renewable sources) to interact with complementary polymers and form novel material structures for use in applications as diverse as wound dressings, graft scaffolds for tissue engineering and bio-sensing in a range of human diseases forms the basis of our ongoing research.
See images: figure 1
Our ongoing research is investigating novel combinations of polymers and peptides for the treatment of chronic inflammation and infection, and novel polymer-growth factor conjugates as adjunctives to stem cell therapy. Successful translation of this research has wide applications, not only in dentistry (e.g. maxillofacial trauma, periodontitis), but shows potential for use in an extensive range of diseases (e.g. diabetic foot ulcers, cystic fibrosis, spinal cord injury).
See images: figure 2
- Pritchard, M. et al. 2016. A new class of safe oligosaccharide polymer therapy to modify the mucus barrier of chronic respiratory disease. Molecular Pharmaceutics 13 (3), pp.863-872. (10.1021/acs.molpharmaceut.5b00794)
- Roberts, J. et al. 2016. In vitro evaluation of the interaction of dextrin-colistin conjugates with bacterial lipopolysaccharide. Journal of Medicinal Chemistry 59 (2), pp.647-654. (10.1021/acs.jmedchem.5b01521)
- Azzopardi, E. A. , Ferguson, E. L. and Thomas, D. W. 2015. Development and validation of an in vitro pharmacokinetic/pharmacodynamic model to test the antibacterial efficacy of antibiotic polymer conjugates. Antimicrobial Agents and Chemotherapy 59 (4), pp.1837-1843. (10.1128/AAC.03708-14)
- Rees, A. et al., 2015. 3D bioprinting of carboxymethylated-periodate oxidized nanocellulose constructs for wound dressing applications. BioMedical Research International 2015 , pp.1-7. 925757. (10.1155/2015/925757)
- Tondervik, A. et al., 2014. Alginate oligosaccharides inhibit fungal cell growth and potentiate the activity of anti-fungals against Candida and Aspergillus spp. Plos One e112518. (10.1371/journal.pone.0112518)
- Ferguson, E. L. et al. 2014. Dextrin-Colistin conjugates as a model bioresponsive treatment for multidrug resistant bacterial infections. Molecular Pharmaceutics 11 (12), pp.4437-4447. (10.1021/mp500584u)
- Powell, L. C. et al. 2014. A nanoscale characterization of the interaction of a novel alginate oligomer with the cell surface and motility of pseudomonas aeruginosa. American Journal of Respiratory Cell and Molecular Biology 50 (3), pp.483-492. (10.1165/rcmb.2013-0287OC)
- McInnes, R. L. et al., 2014. Contrasting host immuno-inflammatory responses to bacterial challenge within venous and diabetic ulcers. Wound Repair and Regeneration 22 (1), pp.58-69. (10.1111/wrr.12133)
- Gethin, D. T. et al., 2014. Studies on the 3D printing of nanocellulose structures. Advances in Printing and Media Technology XLI (1 A2), pp.91-95.
- Roberts, J. L. et al. 2013. An in vitro study of alginate oligomer therapies on oral biofilms. Journal of Dentistry 41 (10), pp.892-899. (10.1016/j.jdent.2013.07.011)
- Azzopardi, E. A. , Ferguson, E. L. and Thomas, D. W. 2013. Colistin past and future: A bibliographic analysis. Journal of Critical Care 28 (2), pp.219.e13-219.e19. (10.1016/j.jcrc.2012.04.008)
- Azzopardi, E. A. et al. 2013. Statistical characterization of succinoylated dextrin degradation behavior in human α-amylase. Journal of Carbohydrate Chemistry 32 (7), pp.438-449. (10.1080/07328303.2013.831434)
- Azzopardi, E. A. , Ferguson, E. L. and Thomas, D. W. 2013. The enhanced permeability retention effect: a new paradigm for drug targeting in infection. Journal of Antimicrobial Chemotherapy 68 (2), pp.257-274. (10.1093/jac/dks379)
- Powell, L. C. et al. 2013. The effect of alginate oligosaccharides on the mechanical properties of Gram-negative biofilms. Biofouling 29 (4), pp.413-421. (10.1080/08927014.2013.777954)
- Khan, S. et al. 2012. Overcoming drug resistance with alginate oligosaccharides able to potentiate the action of selected antibiotics. Antimicrobial Agents and Chemotherapy 56 (10), pp.5134-5141. (10.1128/AAC.00525-12)
- Percival, S. L. et al., 2012. A review of the scientific evidence for biofilms in wounds. Wound Repair and Regeneration 20 (5), pp.647-657. (10.1111/j.1524-475X.2012.00836.x)
- Wildeboer, D. et al., 2012. Specific protease activity indicates the degree of Pseudomonas aeruginosa infection in chronic infected wounds. European Journal of Clinical Microbiology & Infectious Diseases 31 (9), pp.2183-2189. (10.1007/s10096-012-1553-6)
- Wagstaffe, S. J. et al., 2012. Bispecific antibody-mediated detection of the staphylococcus aureus thermonuclease. Analytical Chemistry 84 (14), pp.5876-5884. (10.1021/ac203403d)
|Research Council of Norway (2015-2018)||BIA-Alginates||£3.174,600|
|Research Council of Norway (2015-2018)||Tailored OligoG||£1,032,830|
|Research Council of Norway (2012-2016)||Nanoheal||£1,082,480|
|QBiotics Ltd (2012-2015)||EBC-46||£59,162|
|MRC New Investigator Research Grant (2016-2019)||Accumulation and nephrotoxicity of dextrin-colistin conjugates||£399,982|
Uwch ddarlithydd mewn Therapiwteg Polymer
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