Antimicrobial and nanoparticle penetration and killing in infectious biofilms

Bacterial adhesion to surfaces in the human body can result in biofilm formation, which plays a critical role in bacterial infections. When bacteria adhere to a surface, they start to produce extracellular polymeric substances (EPS), which leads to the formation of a ‘biofilm’. It is estimated that approximately 60% of all bacterial infections are caused by microbial biofilms. One of the problems with biofilm infections is that they can be up to 1000 times more resistant to antibiotic treatment than ‘free swimming’ planktonic bacteria. Biofilms can be up to several millimeters thick, and for the killing of bacteria in a biofilm it is important that antibiotics can penetrate through the full biofilm. Another challenge in the treatment of bacterial infections is the increasing antibiotic resistance of bacteria. Antibiotic resistance of bacteria makes bacterial infections hard or even impossible to treat, because bacteria are less susceptible to antibiotics. Development of new antibiotics or antimicrobials and new delivery strategies of antimicrobials are necessary to combat bacterial infections in the future. Therefore, in this thesis we have explored methods to improve the penetration and killing of antimicrobials and nanocarriers into infectious biofilms. New antimicrobial treatments have been tested on Staphylococcus aureus and Pseudomonas aeruginosa biofilms. Monolaurin lipid nanocapsules with adsorbed antimicrobial peptides (AMPs) and dendritic like polymeric dendrons have been investigated for their biofilm killing and biofilm penetration. In addition, the relation between penetration of antimicrobials and biofilm characteristics has been explored.