Design and testing of microbial responsive nanocapsules

The overall project aim is to create nanoparticle hydrogel composite films for medical devices which can be used for the carriage and active release of antimicrobial moieties and/or signalling dyes. Medical devices including wound dressings, cannulas, catheters etc. will be coated with such films, and designed to give both an early warning of bacterial infection and prevent bacterial growth. The hyaluronic acid shell nanoparticles will be degraded via the action of hyaluronidase, a secretion enzyme of clinically important pathogens including Staphylococcus aureus and Streptococcus pyogenes releasing a dye and /or antimicrobial . Previous work in the Jenkins group has shown that around 98% of these strains (n = 140) secrete significant concentrations of hyaluronidase (sufficient to breakdown hyaluronic acid). Antimicrobials to be studies include: bacteriophage; phage and bacterial lysins; antimicrobial peptides; and small molecule antibiotics.

Once nanoparticles have been synthesised and characterised they will be loaded with cargo and dispersed in a carrier hydrogel matrix, poly vinyl alcohol (PVA). The nanoparticle PVA composite will be coated on two medical devices: wound dressings and urinary catheters. The response of wound dressing prototypes will be tested on both single culture bacterial isolates and then multi-species biofilms designed to model clinical wound environments. Coated urinary catheters will be tested in our in-vitro bladder infection model. The efficacy of the composites will be tested in terms of the dye or antimicrobial release from hyaluronidase secreted by the bacteria and quantitative as well as qualitative microbiology assays carried out. Both infection models are established in the Jenkins group and available for immediate use by George.
The project is inherently inter-disciplinary, comprising primarily polymer chemistry but including full microbiological analysis and workup, and understanding of the clinical problems of medical device infection. To that end we will work with clinical microbiologist from Southmead hospital, Bristol both to inform them of our work and to obtain clinical bacterial isolates for testing in Bath.