Encapsulated phage for treatment of burns and wound site infections

This project, in partnership with Biocontrol Ltd and the departments of Chemistry and Chemical Engineering at the University of Bath, will encapsulate specific lytic phages within phospholipid vesicles, and incorporate the vesicles into a prototype burn / wound dressing and a topical aqueous cream. The primary focus of the work is in the prevention of infection of paediatric burns, where our clinical partner, Dr Amber Young at the South West Paediatric Burns Centre, Frenchay hospital will provide expertise. The vesicles will be designed such that they both will stabilize the phage over time i.e. when stored, but only release their contents following exposure to secreted toxins and enzymes from pathogenic bacteria. The aim of this project is to reduce the risk of infection from burns and other injuries by making a 'smart' dressing, based on phage therapeutics.38,000 children on average suffer burn injuries in England and Wales each year, of which 55% are scalds. Most are small in area, 80% are in children under five years and the majority are due to hot drink spillages. One of the primary problems in the treatment of burns is bacterial infection, which can delay healing, increase pain; increase the risk of scarring and in some cases cause death. In recent years there have been great improvements in the treatment of burns, particularly with biologically-derived dressings which actively promote cell growth. However, the problem of infection has not gone away, and there is evidence that silver treated antimicrobial dressings can delay burn healing.

The development of novel antibacterial technology to reduce morbidity, mortality and healthcare costs due to bacterial wound / surgical site infections and infections of burns is the overarching goal of this project. The four organisms targeted in this proposal are responsible for the majority of infections of burns and wound / surgical site infections and these agents are frequently multiply antibiotic resistant and in some cases may be unresponsive to current antibiotic classes. The problem of infection is especially acute in burns: 38,000 children suffer from burn injuries in the UK each year (Hospital Episode Statistics data 2002). The children's Burn Centre in Bristol admits several hundred such children annually. The clinical concern for these children is mainly one of burn wound infection. One particular infection is Toxic Shock Syndrome an endotoxaemia secondary to S. aureus which has an incidence of 2.5% and, of those that get the full-blown disease, a mortality of up to 50%. Current dressings encourage healing but have no effective anti-bacterial properties. The utilization of naturally occurring phages for delivery to infection sites to replace antibiotic therapy will decrease the selective pressure for the evolution of antibiotic resistant bacteria. This would be particularly pronounced in treating multiply- and pan- antibiotic resistant infections and frequent use of phage therapies would be expected to decrease the burden of antibiotic resistant infections a stated policy aim of health services worldwide. People Scientists working in the fields of chemistry and chemical engineering at University of Bath will be collaborating with life scientists at Biocontrol Ltd to in basic and applied fields and huge potential exists for the cross-pollination of research expertise between these institutions and between the clinical partner and industry partners such as Mlnlycke or Hartman AG. The training of two research students and a postdoctoral researcher in this richly collaborative environment with frequent visits to the relevant institutes will provide a rare mix of different training experiences and skill sets for the funded researchers with exposure to basic and applied research projects for each individual. The association of Biocontrol Ltd with this project will provide opportunities for employment of researchers beyond the funding term of this project in a company that is expanding rapidly having relocated to new laboratories and offices in Colworth Science park in May 2010. Economy Biocontrol Ltd is currently almost entirely investor funded although small grants have been secured from smaller charities and regional development funds in the past including the European Cystic Fibrosis Society. The company's phase I/IIa clinical trials in animals and humans have been self-funded but larger scale, phase III trials will require substantial external investment which will be attracted by dissemination of the achievement of the basic and applied research goals of the work packages in this proposal. , The award of this grant in itself will help attract funding for the company's laboratory and clinical studies with the prospects for the future employment of research and development scientists and other personnel in the future. With the exception of P. aeruginosa the company's work on the three other organisms named in this proposal has thus far been under-exploited - the potential for phage products to treat S. aureus, A. baumannii and K. pneumonia would be expected to target part of a global annual multi-billion dollar market for anti-infectives.