Design and self-assembly of guanidinium-functionalized polycarbonates for increased selectivity towards pathogenic bacteria

Abstract

Guanidinium-functionalized amphiphilic polycarbonates have recently been proven to be effective in treating infections caused by multidrug resistant bacteria. These positively charged polymers are able to electrostatically interact with the negatively charged microbial membrane, before translocating across to kill the microbe by targeting intracellular proteins and genetic materials. The design of these polymers has been tricky as it is imperative to find the right amphiphilic balance. It is common to increase their hydrophobicity for a more efficient antimicrobial activity. However, at elevated levels of hydrophobicity, they also indiscriminately disrupt healthy mammalian cell membrane due to enhanced membrane affinity. Moreover, due to their cationic nature, they often interact with the anionic salic acid, found on the surface of red blood cells, resulting in hemagglutination. This has hampered their in vivo application. In this thesis, we address these issues by looking at strategies to improve the selectivity and biocompatibility of these polymers.