Synthesis of amphiphilic antimicrobial polymer-antibiotic conjugates and particle networks

Abstract

In previous work by Martin Schmidt^1 in 2018, it was found that amphiphilic polymer systems based on poly(2-oxazolines) (POx) could be successfully conjugated to the antibiotic ciprofloxacin (CIP). These amphiphilic polymer-antibiotic conjugates (PACs) led to the enhanced activity of the antibiotic CIP. In this work, these amphiphilic PAHs were taken up and further investigated for their exact mode of action. Thus, the mode of action of the additional induced membrane activity by the amphiphilic polymer system on the activity of the antibiotic was investigated. A crucial factor is the dependence of the amphiphilic PACs on the hydrophobic/hydrophilic balance (HHG) of the POx tail. Continuation of the mechanistic investigations led to the consideration of replacing the hydrophobic part of the amphiphilic poly(2-oxazoline) block copolymers with a biocompatible naturally occurring substance. In doing so, poly(2-methyl-2oxazoline) (PMOx) should remain as the hydrophobic moiety. The purpose of this consideration is to improve the biocompatibility of amphiphilic PACs and lower blood and cell toxicity. Furthermore, also based on the results of Martin Schmidt^1, the reversible crosslinking of polymer-antibiotic conjugates with amphiphilic ABA triblock copolymers was investigated at the molecular level. It was already known that PACs based on hydrophilic and hydrophobic poly(2-oxazolines) form worm micelles that are very stable and strongly activate the conjugated antibiotic. Further, the exact interaction of the PACs with the ABA triblock copolymers should be investigated and explored to understand the exact background for the controlled and switchable antimicrobial effect of the antibiotic.