Grŵp Therapïau Uwch
The work of the group is focused on polymer therapies derived from nature in applied research.
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 a range of difficult to treat, often life-threatening infections.
The work of the group is focused on polymer therapies derived from nature in applied research.
- To investigate novel antimicrobial therapies, such as low molecular weight alginates and epoxytiglianes, and tailor them to optimise their maximum potential therapeutic effect against multi-drug resistant bacteria, yeasts and viruses.
- To develop 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.
- To characterise the antimicrobial potential of novel chronic wound dressing materials such as nanocellulose.
- AlgiPharma AS, Sandvika, Norway.
- Qbiotics Ltd, Brisbane, Australia.
- SINTEF Materials and Chemistry, Trondheim, Norway.
- Norwegian University of Science and Technology (NTNU),Trondheim, Norway.
- ERASMUS University Rotterdam, Netherlands.
- UCL Great Ormond Street Institute of Child Health, London, UK.
- National University of Singapore, Singapore.
- Cultech Ltd, Port Talbot, UK.
- Centre for Nanohealth, College of Medicine, Swansea University, UK.
- Venture Life Group plc, Bracknell, UK.
Low molecular weight alginates from marine algae to treat chronic respiratory disease
Industrial partnership: AlgiPharma AS, Norway
We have been involved in the development of antimicrobial and anti-biofilm polymer therapies based on a low molecular weight alginate oligosaccharide, derived from seaweed since 2007 Our subsequent research has been a key part in the optimisation of the delivery of OligoG CF-5/20 (Fig 1), as a dry powder inhalation therapy for cystic fibrosis patients (currently in Phase IIb/III clinical trials). We are extending this research as part of a multi-national collaborative research grant, we are currently looking into innovative approaches to improve drug bioavailability through more effective drug delivery, reduced toxicity, better dosing regimens and improve drug stability during translocation across the mucosal barrier (respiratory, intestinal and genito-urinary) to the target site. This research has been funded by AlgiPharma AS, the European Social Fund, the Cystic Fibrosis Foundation and the Research Council of Norway.
Figure 1. Deposition of OligoG CF-5/20 in the CF lung. (a) Deposition of a radio-labelled OligoG CF-5/20 DPI formulation (Dry Powder for Inhalation) in the lungs of a CF patient (a) anterior and (b) posterior view. View publications. Further permissions related to the material excerpted in this figure should be directed to the ACS.
Modifying bacteria and biofilm behaviour to improve clinical wound healing outcomes using novel compounds derived from the Australian rain forest
Industrial partnership: QBiotics Ltd, Australia
We are investigating the therapeutic effect of semi-synthetic epoxytigliane compounds generated from the Blushwood tree found in the Queensland rainforest. Work by our group and our collaborators at QIMR in Brisbane, has shown that these molecules can modify the behaviour of Gram-positive multi-drug resistant (MDR) and oral pathogens, allowing diffusion through biofilm matrices and disrupting biofilms. The first in vivo studies using EBC-1013 (the lead candidate; Fig 2) have demonstrated the ability of these agents to improve the healing of chronic diabetic skin wounds. This research has been funded by Qbiotics Ltd and the Welsh Assembly Government
Figure 2. Molecular dynamics simulations (MDS) showing molecular representations of (a) EBC-1013 ligand interactions; (b) EBC-1013 embedded on the surface of the PAO1 cell outer membrane (LPS-DPPE) bilayer. (Powell et al 2021).
Industrial partnerships: AlgiPharma AS, Norway; Cultech Ltd, United Kingdom
The Advanced Therapies Group have proven expertise in the use of natural biodegradable polymers (e.g. polysaccharides) as novel carriers for proteins, peptides and drugs. Attachment of biodegradable polymers can improve drug targeting to sites of inflammation, thereby minimising toxicity, overcoming resistance and increasing bioavailability (Fig 3). Notably, dextrin-epidermal growth factor (EGF) conjugates developed in our group were the first polymer therapeutics for tissue repair and the first paper from this work was featured as the cover story of the Journal of Controlled Release. These pioneering studies opened up a wealth of new opportunities for bioresponsive drug delivery in tissue repair and regeneration. We have since demonstrated the benefits of using polymer conjugation for the treatment of chronic inflammation and infection, for simultaneous targeting of cancer and bacterial infections, and to support growth and differentiation of neural stem cells. In collaboration with AlgiPharma AS, we developed the first bi-functional polymer therapeutics to significantly enhance the efficacy of antibiotics. This research has been supported by collaborations with leading figures in nanomedicine and biological sciences and by highly competitive funding sources (e.g. Medical Research Council, Wellcome Trust, Royal Society, Research Council of Norway, Science and Technology Funding Council, European Social Fund (ESF) and Welsh Assembly Government).
Please see Dr Elaine Ferguson's profile for further details of current projects.
Figure 3. Schematic showing the proposed mechanism of action of polymer conjugates based on natural biodegradable polymers.
Anti-viral activity of mouthwash against COVID-19 (MOMA)
Industrial partnership: Venture Life Group PLC
Salivary spit from the mouth and throat of coronavirus patients contains a high viral load in early infection. The spread of virus by contaminated saliva is a major risk for healthcare workers caring for these patients. Studies have shown that several mouthwashes are able to kill viruses similar to coronavirus in the mouth and throat. Laboratory tests have also indicated that certain components in mouthwashes are able to affect the coronavirus fatty “coating”. In association with Venture Life Group PLC, a clinical trial was set up to investigate if the use of mouthwash in coronavirus (COVID-19) patients can reduce the amount of virus contained within saliva. The mouthwash could be used to reduce the risk of spreading the virus to healthcare workers during a procedure involving the mouth. This research has been funded by Venture Life Group PLC.
Bacteriocin Production by Probiotic Bacteria
Industrial partnership: Cultech Ltd, Port Talbot, Wales
In association with the probiotics company Cultech Ltd, we have been investigating natural antimicrobial peptide production (bacteriocins) by probiotic lactic acid bacteria with a view to improving and optimising commercial production of mixed-population probiotics. This research has been funded by Cultech Ltd and the European Social Fund.
Current funding (in descending financial order)
MRC New Investigator Research Grant
Accumulation and nephrotoxicity of dextrin-colistin conjugates
Norwegian Research Council
Mucos-ALG: Development of novel alginate oligomers for enhanced delivery across mucosal barriers
Investigating epoxytiglianes as novel anti-biofilm therapeutics for a range of wound healing and anti-infective applications
Sêr Cymru II Fellowship
The development of in vitro models of respiratory biofilm assembly to develop novel antimicrobial therapies
Characterisation of novel epoxy-tigliane therapeutics in treatment of multi-drug resistant (MDR) wound and implant infection
European Social Fund
Developing novel technologies to model the effects of therapies on bacterial biofilms
Venture Life Group PLC
Measurement of mouthwash anti-viral activity against COVID-19 (MOMA)
Medical Research Council
Confidence in Concept: Potential of lactobacillus spp.-derived polysaccharides as novel bi-functional carriers in polymer conjugates
Wellcome Trust ISSF3 Translational Kickstart award
Development of a nanomedicine approach for simultaneous targeting of cancer and bacterial infections
Sêr Cymru Infrastructure accelerator award
Gel imaging system for multidisciplinary use in School of Dentistry, Cardiff University
- ISRCTN25647404 : Measurement of the effect of mouthwash against COVID-19 (MOMA) (2020)
- Phase IIb/III: A Dose-finding Study of Inhaled OligoG vs Placebo in Patients With Cystic Fibrosis NCT03698448 (2020)
- Phase IIb: A phase 2b randomised placebo-controlled study of OligoG in patients with cystic fibrosis NCT03822455 (2019)
- A Study of OligoG in Cystic Fibrosis Subjects With Burkholderia Spp. Infection (SMR-2591) NCT02453789 (2015)
- Phase IIb: A Phase IIb study of OligoG in Subjects With Cystic Fibrosis (SMR-2984) OligoG NCT02157922 (2014)
- Phase II: A Study to Investigate Lung Deposition of Radiolabelled OligoG NCT01991028 (2014)
- Phase I/II: A Cross-over Study of OligoG in Subjects With Cystic Fibrosis NCT01465529 (2011)
- Phase I: Safety and Efficacy of Inhaled OligoG CF-5/20 for the Treatment Cystic Fibrosis NCT00970346 (2009)
- Alginate oligomers for use in overcoming multidrug resistance in bacteria US9801901B2
- Use of alginate oligomers in combating biofilms US10624920B2
- Anti-microbial alginate oligomers WO2010139958A1
- Therapeutic conjugates WO2012035310A2
- Bacitracin-alginate oligomer conjugatesWO2018073448A1
- Polymyxin-alginate oligomer conjugates AU2017345295A1
- Method for wound healing US20160317486A1
Cwrdd â'r tîm
- Powell, L.C., Abdulkarim, M., Stokniene, J. et al. Quantifying the effects of antibiotic treatment on the extracellular polymer network of antimicrobial resistant and sensitive biofilms using multiple particle tracking. npj Biofilms Microbiomes 7, 13 (2021). Read more here.
- OakleyJ et al. 2021. Phenotypic and genotypic adaptations in Pseudomonas aeruginosa biofilms following long-term exposure to an alginate oligomer therapy mSphere, 6:e01216-20. Read more here.
- O’Donnell VB et al 2020. Potential role of oral rinses targeting the viral lipid envelope in SARS-CoV-2 infection. Function, 1, zqaa002. Read more here.
- Stokniene, J. et al. 2020. Bi-Functional alginate oligosaccharide–polymyxin conjugates for improved treatment of multidrug-resistant Gram-negative bacterial infections. Pharmaceutics 12, 1080. Read more here.
- Yang, Q. E. et al. 2020. Compensatory mutations modulate the competitiveness and dynamics of plasmid-mediated colistin resistance in Escherichia coli clones. ISME J 14, 861-865. Read more here.
- Varache, M. et al. 2019. Polymer masked-unmasked protein therapy: Identification of the active species after amylase-activation of dextrin-colistin conjugates.. Mol Pharm 16, 3199-3207. Read more here.
- Jack, A. A. et al. 2019. Cellulose nanofibril formulations incorporating a low molecular weight alginate oligosaccharide modify bacterial biofilm development. Biomacromolecules 20, 2953-2961. Read more here.
- Ferguson, E. et al. 2020. Polysaccharides for protein and peptide conjugation. In: Pasut, G. and Zalipsky, S. eds. Polymer-Protein Conjugates: From Pegylation and Beyond. Elsevier, pp. 421-453. Read more here.