| dc.description.abstract | Because of the limited number of antibiotics available and the similarities in their activity and mode of action, considerable nonclinical and clinical research is being spent in the discovery and development of new and non-conventional anti-infective medicines. Interestingly, the polymyxins have piqued the interest of researchers as promising new antibiotics to control infectious pathogens arising from MDR Gram-negative bacteria. In reality, only a few polymyxins have been utilized in “real-world” application, with the most clinically relevant being colistin. While efficacious in the clinical setting, there were subsequent studies that reported severe toxicities with use of colistin as a therapeutic option, especially nephrotoxicity and neurotoxicity as uncommon adverse event The disadvantages associated with colistin can be mitigated by encapsulating the peptide in nanocarriers like block copolymer micelles. However, there is a scarcity when it comes to core-shell assemblies by peptide-polymer conjugates, and in particular the assemblies of peptides assembled with neutral-polyanion DHBC. Moreover, the relation between the release of the peptide and the nanocarrier structure and dynamics is lacking. Therefore, the overall aim of the research presented in this thesis was to develop novel nanomedicines based on the peptide colistin. This includes a systematically investigation of the phase diagram of colistin/PEO-b-PMAA mixtures as a function of pH, charge ratio and total concentration. The overall goal will be to find optimal conditions under which stable core-shell colistin-polymer complexes are formed. In the second part of the project, different formulations of colistin-polymer nanoparticles where investigated in vitro for their bacterial killing activity against few multidrug-resistant Gram-negative bacteria isolates, which were compared to that of free colistin. | eng |