Enzyme-Degradable Polyion-Complex (PIC) Particles for the Treatment and Detection of Pseudomonas aeruginosa

Project Information

AntibioPICs

Grant agreement ID: 747801

DOI

10.3030/747801

Project closed

EC signature date 13 March 2017

Start date 12 March 2018

End date 31 May 2020

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 195 454,80

EU contribution

€ 195 454,80

Coordinated by

THE UNIVERSITY OF BIRMINGHAM
United Kingdom

Periodic Reporting for period 1 - AntibioPICs (Enzyme-Degradable Polyion-Complex (PIC) Particles for the Treatment and Detection of Pseudomonas aeruginosa)

Reporting period: 2018-03-12 to 2020-03-11

Summary of the context and overall objectives of the project

In this project we had developed (nano)particles that can selectively release relevant antibiotic only if a pathogenic bacterial caused infections.

Two exemplars had been explored:

1. Targeted delivery of polymyxins, antibiotic peptides currently used in the clinic as last resort antimicrobials.
2. Targeted delivery of imaging agents, to label microbial membranes in the infection site.

the importance of our research comes from the fact that it addressed current challenges in antimicrobial research and in the development of new antibiotic targeting the multidrug resistance bacteria called superbugs. in particular: 1) the development of better methods to use currently available antibiotics.
2) the early detection of bacterial infections.

The project objectives were:
1. Synthesis of enzyme Degradable Polymer to facilitate antibiotic encapsulation in nanoparticles called PIC particles.
2. Preparation of enzyme Degradable Polymer to facilitate FM® 1-43 Dye encapsulation in nanopartiCharacterisation of PIC particle stability and enzyme-degradation kinetics and selectivity
3. In-vitro evaluation of 1) antimicrobial activity of the prepared nanoparticles against pathogenic bacteria called P. aeruginosa and 2) ability of the FM-containing particles to stain and report the infection caused by this bacteria P. aeruginosa with colour change to naked eye.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

In this project, we targeted P. aeruginosa, an opportunistic pathogen that is currently treated with polymyxins, and pseudolysin, a major virulence factor of this pathogen.
The project has been divided into the next work packages (WP).
WP1. Synthesis of Pseudolysin-degradable polymer and incorporated polymerisable moieties into pseudolysin-degradable peptides to facilitate the synthesis of high molecular weight polymers that carry the required charge density. later the degradations of these polymers were studied against Enzymes Thermolysin Elastase (THE) or Human Leucocyte Elastase (HLE). The result confirmed that our system from polymer and the encapsulated antibiotic was stable under physiological conditions and only get degraded and release the antibiotic only in the presences of the pathogenic bacteria and only in the infection site. Besides our studies suggested that these nanoparticles are less toxic than the free antibiotic and more effective because it cause localized delivery of the antibiotic close to these bacteria that hence it's antimicrobial effect.
The obtained results are very important and the beneficiary has done several discussion and exploration of these results in several conferences, public outreach and workshops.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Inovation capacity impact of the project results
The prepared nanoparticles from enzyme-responsive PIC particles for the delivery of antibiotic as Polymixin; last-resort antibiotics against multi-resistant s bacteria. These results will contribute to develop new tools to fight against antimicrobial resistance, one of the biggest medical challenges and a research priority for the European Commission (EC) this time.
The research results, we believe it can underpin future applications in both academia and industry, and therefore a future financial gain for the European Research Area (ERA). This technology potentially will be used for target other relevant infected bacteria. This programme had delivered unique world-leading research that will allow the development of functional nanomaterials that will be especially suited in the prevention and management of colonisation of wounds and medical surfaces by pathogenic bacteria in the next few years. This 2-year project led to very important scientific results that are under preparation for publishing in a high-quality scientific journal with open access.



Scientific and technological quality of the results

In details, we present nanoparticles particles as a specific delivery system for the antimicrobial antibiotics Polymyxin B with no need for any chemical modification. The prepared nanoparticles were degraded and release the antibiotic in a specific and selective way only in the presence of infections. This work had done in this project by the beneficiary and the supervisor will open a new way for a new type of antimicrobial materials that will help in fighting against these antibiotics resistances bacteria and decrease the possibility of resistance development to this antimicrobial formulation over time. As in this case, we had chosen P. aeruginosa; opportunistic pathogenic bacteria, known to commonly associated with more than 20% of hospital infections, able to be colonised in wounds and immunocompromised patients.

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