Non-Targeting and Self-Targeting Novel Nano-Antimicrobials In Vitro and In Vivo

Microbial infections are becoming a growing threat to public health, due to the development of increasing numbers of microbial strains that are multi-drug resistant. Contributing to this threat is the fact that most infections present themselves as microorganisms growing in a biofilm that is recalcitrant to penetration of most antimicrobials. In recent years, various nanotechnology-based antimicrobials have been developed to kill antibiotic-resistant microorganisms in a planktonic-mode of growth leaving the question of efficacy against microorganisms in a biofilm-mode of growth. This quest, although necessary, can be considered futile as microorganisms seem to be able faster and faster to achieve resistance against new antimicrobials. Therefore, focusing on breaking down the biofilm barrier to antimicrobial penetration using existing antimicrobials might be a more worthwhile goal. For the past years, new nanotechnology-based antimicrobials, including several new ways have been designed to encapsulate existing antimicrobials to combat biofilm-infections. Smart encapsulation methods allow self-targeting of the nanocarrier to an infection site upon an environmental trigger, i.e. mostly a pH trigger. In this thesis, we developed novel nano-antimicrobial concepts based on non-targeting and self-targeting antimicrobial carriers for the control of infectious biofilms, not only including bacterial biofilms but also relatively forgotten fungal biofilms. Evaluation of the efficacy of the concepts developed was done in vitro and in animal models for new nano-antimicrobials that are fully non-targeting to dual-responsive, self-targeting nano-antimicrobials. In the general discussion of this thesis, the merits of non-targeting and self-targeting nanocarriers were also compared