Polycaprolactone based clickable nano-assemblies for antimicrobial activity

Abstract

Microbial infection is an all-time threat to global public health which includes the ever-increasing infections caused by bacteria, parasites, viruses and fungi. The scientific community have been developing various strategies and techniques to tackle microbial infections and help us build a healthy community. The microbes developing drug resistance have always been a problem for us, there comes the importance of cationic polymeric compounds as promising candidates for anti-microbial agents with a decreased potential for resistance development. Along with its intrinsic antimicrobial action through membrane permeabilization, the polymeric matrix is also responsible for encapsulating antibiotics for dual action. This MS Project is directed towards the study of polycaprolactone based Biodegradable Cationic block copolymers. We aim to develop a PEGylated cationic polycaprolactone polymer for enhanced solubility, decreased immunogenicity and boost the pharmacokinetic behaviour of the cationic nano-assembly. Along with this, we are also trying to bring the concept of ‘click chemistry’ for the synthesis of these cationic polymers. PEG-5K monomethyl ether and tri-ethylene glycol monomethyl ether were used as the initiators for successful ring-opening polymerization of an alkyne substituted caprolactone monomer which was further clicked with a halogen bearing small molecule and then quaternized with triethylamine to form PEG-containing cationic polymers. PEG was utilized to improve the selectivity of the cationic polymers towards bacterial over mammalian cells. The quaternized polymers were checked for antibacterial activity and we got 80% killing in 50 microgram/mL concentration of the block copolymer whereas homo polymer showed no killing. To make the direct visualization of this antimicrobial activity possible, we also developed an azide functionalized fluorophore conjugate which can be attached to the polymeric backbone through click reaction.