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Polyion complex (PIC) nanoparticles for the targeted and passive delivery of antimicrobial polymers and peptides
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Polyion complex (PIC) nanoparticles for the targeted and passive delivery of antimicrobial polymers and peptides
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Dissertation
Polyion complex (PIC) nanoparticles for the targeted and passive delivery of antimicrobial polymers and peptides
2017
Overview
Antibiotic resistance is a serious worldwide threat. Alternative solutions to the limited pipeline of new antibiotics are urgently needed. Nanotechnology and drug delivery can be used to develop new therapies from old antimicrobials by controlling their distribution in the body. The goal of this thesis was to investigate the formation and activity of polyion complex (PIC) nanoparticles as vehicles for the delivery of two cationic antibiotics: poly(ethylene imine), used as model to develop these nanomaterials, and the FDA-approved antimicrobial peptide polymyxin B. These antibiotics were combined with two types of polyanions to form PIC particles with distinct antimicrobial properties: 1) Anionic peptides, degradable by bacterial enzymes led to bacteria-targeted nanoparticles; 2) Acidic polymers assembled particles for passive release, which tuned the activity of the antibiotic in the absence of a specific trigger. All the PIC particles prepared were characterised, and their physiological stability and antimicrobial properties evaluated. To improve the stability and activity of these nanoparticles, several characteristics of their anionic components were optimised: 1) their multivalency, as a function of the peptide’s anionic residues and polymer’s DP; 2) the acidity of the polymers; and 3) the number of cross-linking residues in the peptides.
Publisher
ProQuest Dissertations & Theses
Subject
