Biofilm disruption as an initial step in a novel strategy for treatment of chronic wounds based on multi-functional liposomal nanocarriers

The cost to the NHS of caring for patients with chronic wounds is conservatively estimated to be £4.5-5.7bn/year, or around 4% of the total expenditure on health. One important element in the microbial colonization of chronic wounds is the presence of biofilms, where bacteria are organised into complex community structures composed of bacterial cells surrounded by extracellular polysaccharides. Bacteria in biofilms are up to 500 times more resistant to conventional antimicrobial treatments than when in their free-floating form, as biofilms can present a physical barrier to the access and so bioavailability of antimicrobial agents. Biofilms are produced by most chronic wound pathogens e.g., Staphylococcus aureus (incl. MRSA), and Pseudomonas aeruginosa. Thus, any successful and innovative wound healing strategy needs to tackle this issue.

Significant efforts are being made to develop efficient technologies for wound care. Of these, liposomal formulations show promise as topical drug delivery systems. They attempt to address the twin goals of reaching and acting on the infection and damaged wound tissue, as well as provide an optimal environment to aid cell growth and migration. The advantages include their similarity to cell membrane phospholipid domains (and thus ability to support cell repair), providing a moist molecular film to promote epithelialization, and ability to facilitate the targeted release of an anti-microbial via their direct contact with microorganism cell membranes.
In this project, novel topical liposomal nanocarriers capable of converging selectively and deeply into the infection site, and loaded with a biofilm disruptor, will be developed. By degrading the biofilm, the efficacy of antimicrobial drugs will be increased at the wound site.

This should efficiently debulk the bacterial load thus expediting the wound healing process. Techniques which will be involved in the project include development and preparation of liposomal nanocarriers, and evaluation in both in vitro and in vivo experimental models of biofilms and chronic wounds.

This multidisciplinary project sets out to optimise the 1st step of what will ultimately be a multi-step strategy to manage bacterial numbers in chronic wounds. Even without development of further steps, this step alone will contribute to improving current wound management strategies.