Antibacterial Polymers Based on Poly(2-hydroxyethyl methacrylate) and Thiazolium Groups with Hydrolytically Labile Linkages Leading to Inactive and Low Cytotoxic Compounds.

Rocío Cuervo-Rodríguez,Marta Fernández-García,Alexandra Muñoz-Bonilla,Fátima López-Fabal

doi:10.3390/ma14237477

Abstract

Herein, we develop a well-defined antibacterial polymer based on poly(2-hydroxyethyl methacrylate) (PHEMA) and a derivative of vitamin B1, easily degradable into inactive and biocompatible compounds. Hence, thiazole moiety was attached to HEMA monomer through a carbonate pH-sensitive linkage and the resulting monomer was polymerized via reversible addition-fragmentation chain transfer (RAFT) polymerization. N-alkylation reaction of the thiazole groups leads to cationic polymer with thiazolium groups. This polymer exhibits excellent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) with an MIC value of 78 µg mL−1, whereas its degradation product, thiazolium small molecule, was found to be inactive. Hemotoxicity studies confirm the negligible cytotoxicity of the degradation product in comparison with the original antibacterial polymer. The degradation of the polymer at physiological pH was found to be progressive and slow, thus the cationic polymer is expected to maintain its antibacterial characteristics at physiological conditions for a relative long period of time before its degradation. This degradation minimizes antimicrobial pollution in the environment and side effects in the body after eradicating bacterial infection.

Highlights

In recent years, the development of new antibacterial materials has attracted increasing attention as antibiotic resistant infections are becoming one of the most healthcare challenges facing the world [1]
Antibiotics in sub-lethal levels found in soil, rivers, lakes, drinking water, etc., can promote the presence of antibiotic-resistant genes (ARGs) in the environment contributing to bacterial resistance to antibiotics [3,4]
In the design of the antibacterial polymer based on biocompatible poly(2-hydroxyethyl methacrylate) (PHEMA), cationic thiazolium groups derived from vitamin B was incorporated within the structure through a pH-labile carbonate ester linkage

Summary

Introduction

The development of new antibacterial materials has attracted increasing attention as antibiotic resistant infections are becoming one of the most healthcare challenges facing the world [1]. The overuse of antibiotics by humans, animals and in agriculture is considered one of the main causes of antimicrobial resistance development (AMR) This antibiotic consumption is continuously growing and is responsible for the increased antibiotic pollution in the environment [2]. Antibiotics in sub-lethal levels found in soil, rivers, lakes, drinking water, etc., can promote the presence of antibiotic-resistant genes (ARGs) in the environment contributing to bacterial resistance to antibiotics [3,4] These environmental concerns have to be taken into consideration in the design of new antibacterial agents in order to reduce antibiotics pollution [5,6,7,8]. In the few last years, a large number of new synthetic polymers

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Conclusion