Abstract
Here we present new enzyme-responsive polyion complex (PIC) nanoparticles prepared from antimicrobial poly(ethylene imine) and an anionic enzyme-responsive peptide targeting Pseudomonas aeruginosa's elastase. The synthetic conditions used to prepare these nanomaterials allowed us to optimise particle size and charge, and their stability under physiological conditions. We demonstrate that these enzyme responsive PIC nanoparticles are selectively degraded in the presence of P. aeruginosa elastase without being affected by other endogenous elastases. This enzyme-responsive PIC particle can exert an elastase-specific antimicrobial effect against P. aeruginosa without affecting non-pathogenic strains of these bacteria. These targeted enzyme-responsive PIC nanoparticles constitute a novel platform for the delivery of antimicrobial peptides and polymers, and can be a powerful tool in the current race against antimicrobial resistance.
Highlights
There is an increasing concern with the emergence of microbial strains that can resist the action of current antimicrobials.[1,2,3] As evidenced over the last decades, the limited pipeline of new antibiotics cannot cope with this increasing number of resistant microbes,[4,5,6] and new antimicrobial strategies are needed that go beyond the development of new drugs.[7,8] One such strategy is the re-evaluation of drug candidates, which have been discarded due to toxicity and side effects
The synthetic conditions used to prepare these nanomaterials allowed us to optimise particle size and charge, and their stability under physiological conditions. We demonstrate that these enzyme responsive polyion complex (PIC) nanoparticles are selectively degraded in the presence of P. aeruginosa elastase without being affected by other endogenous elastases
We have developed an easy methodology for the preparation, under aqueous conditions, of PIC nanoparticles from an enzyme-responsive anionic peptide and a cationic antimicrobial polymer
Summary
There is an increasing concern with the emergence of microbial strains that can resist the action of current antimicrobials.[1,2,3] As evidenced over the last decades, the limited pipeline of new antibiotics cannot cope with this increasing number of resistant microbes,[4,5,6] and new antimicrobial strategies are needed that go beyond the development of new drugs.[7,8] One such strategy is the re-evaluation of drug candidates, which have been discarded due to toxicity and side effects. Despite being powerful antimicrobial agents, the widespread use of antimicrobial peptides in the clinic is limited by their inactivation by serum proteases, toxicity to eukaryotic cells and high production cost.[9,10,11] The positively-charged amphiphilic structure of antimicrobial peptides is responsible for damaging bacterial membranes and cytosol components, resulting in a fast and multi-target antimicrobial action with
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