Bridging the Gaps: Systems-level approaches to antimicrobial resistance
Biodegradation of biodegradable materials in vitro and in vivo
Phil Hill (Biosciences), Roger Bayston (Medicine), Jonathan Wattis (Mathematical Sciences), Neil Thomas (Chemistry), Dirk Grijpma (University or Twente (NL)
Biodegradable drug delivery polymers are used to treat localised infection because they allow antibiotics to be delivered directly in to surgical wounds. They have advantages over using traditional prophylactic antibiotics such as tablets and IV antibiotics because:
- Greater concentrations of antibiotic can be used because the treatment is localised and doesn’t cause the same toxicity risk to the patient’s liver and kidneys
- The ratio of drugs reaching bacteria can be better controlled to maximise synergy
- There is no requirement for drug to be bioavailable (in circulation in the blood stream) so we might see improved pharmacodynamics (what the drug does to bacteria) without compromising pharmacokinetics (what the body does to the drug)
- It is important to control the rate at which antibiotics are released because treatment can fail if antibiotics are released too slowly or too quickly. If the polymer used degrades too fast, delivery of antibiotics might speed up and the therapy might fail.
The project intends to begin answering the following questions:
- How and at what rate do biodegradable polymers degrade in vivo (in animal subjects) compared to in vitro (in “test tube” study)?
- Is the rate affected by enzymes produced by bacteria?
- How does this affect release rates of antimicrobials in the polymers?
- Researchers will use the target polymer poly(trimethylene carbonate) (PTMC) to study antibiotic release and the inhibition of Staphylococcus aureus, using CT imaging, radio-labelled markers and mathematical modelling.
This study at The University of Nottingham is novel because degradation rates and antibiotic release have been more commonly studied in vitro, and in vivo studies have not factored in the contribution from bacterial enzymes. This feasibility study, and any follow-up studies, will impact on antimicrobial resistance because if polymers can be optimised to increase the effectiveness of antibiotics at the surgery site, fewer antibiotics will be used throughout treatment. Optimal early treatment of potential surgical infections also decreases the chance that the patient will need broad-spectrum antibiotics later on. High antibiotic use is a known contributor to the increase in antimicrobial resistance and optimal treatment for surgical wounds both reduces the antibiotic load on the patient and the levels of active antibiotics passing in to the sewage system where it can elicit resistance.
If you are interested in finding out more about this research or about Bridging the Gaps please be in contact with Harry Moriarty firstname.lastname@example.org in the first instance.