The problem we have been aiming to solve or, at the least, greatly alleviate, concerns the strong resistance to drug delivery, and hence to treatment and cure (eradication), of bacterial biofilm infections, which impose a large economic and health burden. This is done by exploiting a recent discovery concerning the properties of certain functionalized liposomes, i.e. vesicles whose membranes are lipid bilayers.
Pathogenic bacteria in the form of microbial biofilms, which form both at infections in vivo and on devices in contact with living tissue, are structured as communities which encase themselves in a dense hydrated matrix of polysaccharide and protein. This matrix strongly suppresses penetration of antibiotics to the bacteria, rendering them highly resistant to drug treatment. This resistance, and the limited success in overcoming it to date, constitutes the major objectives which this project addresses.
Because of their resistance to existing antibiotic-delivery systems, treatments available for wound infections are poorly efficient and very side-effects prone. There is therefore an urgent need for vehicles which enable efficient delivery of the drugs directly to the bacterial pathogens at the infected sites. In this context, lipid-bilayer vesicles, or liposomes, in particular have been proposed as suitable drug delivery nanovehicles, not least for bacterial infections, with their versatility arising from biocompatibility, ability to incorporate both water-loving and water-hating compounds (in contrast to micellar or polymer nanoparticle vehicles where such duality is considerably more challenging), and protection of their cargo prior to delivery. Such liposomic vehicles are most often functionalized by poly(ethylene glycol) moieties (PEG, the current gold-standard)) both for colloidal stability and, in the case of IV administration, to increase their blood circulation time through steric suppression of protein adsorption. Such PEGylation, however, is itself associated with significant problems, greatly reducing their efficiency for biofilm treatment.
Our solution to the above problem of suppressed drug delivery to bacterial biofilms is to implement a new functionalization strategy for liposomic drug carriers, by replacing the generally-used PEG moieties on liposomes with novel (IP-protected) biocompatible moieties, provides colloidal stability to the liposomal dispersions comparable to PEGylation, with extended shelf-life (more than one year). Crucially, however, it is expected to provide significant advantages relative to PEGylation for drug delivery to the bacterial cells in biofilms. This arises from the specific structure of the functionalizing groups on the liposomes, which . There is also independent evidence that novel functionalized lipid vesicles we use do not adsorb plasma proteins and so are likely not to readily trigger an immune response, resulting in long circulation time.
In this way the project creates novel drug-delivery vehicles based on drug-encapsulating functionalized liposomes, which can be used to treat drug-penetration-resistant bacterial biofilm infections far more efficiently than existing drug-delivery solutions, leading to their eradication. The implications of this are that a major health burden affecting millions, with large economic costs will be strongly alleviated.
