Synthesis and Antibacterial Study of Sulfobetaine/Quaternary Ammonium-Modified Star-Shaped Poly[2-(dimethylamino)ethyl methacrylate]-Based Copolymers with an Inorganic Core

Abstract

Cationic polymethacrylates are interesting candidates for bacterial disinfectants since they can be made in large-scale by various well-established polymerization techniques such as atom transfer radical polymerization (ATRP). However, they are usually toxic or ineffective in serum and various strategies to improve their biocompatibility or nonfouling property have often resulted in compromised bactericidal activity. Also, star-shaped polymers are less explored than linear polymers for application as antibacterial compounds. In this paper, star polymers with poly[2-(dimethylamino)ethyl methacrylate] (PDMA) as the arms and polyhedral oligomeric silsesquioxane (POSS) as the core (POSS-g-PDMA) were successfully synthesized by ATRP. The minimum inhibition concentrations (MICs) of the synthesized POSS-g-PDMA are in the range of 10-20 μg/mL. POSS-g-PDMA was further modified by various hydrophilization strategies in attempting to reduce hemolysis. With quaternization of POSS-g-PDMA, the antibacterial activities of the obtained quaternary polymers are almost unchanged and the copolymers become relatively nonhemolytic. We also copolymerized sulfobetaine (SB) with POSS-g-PDMA to obtain random and block PDMA-co-PSB arm structures, where the PDMA and poly(sulfobetaine) were the cationic and zwitterionic blocks, respectively. The random cationic-zwitterionic POSS-g-(PDMA-r-PSB) copolymers showed poor antibacterial activity, while the block POSS-g-(PDMA-b-PSB) copolymers retained the antibacterial and hemolytic activity of the pristine POSS-g-PDMA. Further, the block copolymers of POSS-g-(PDMA-b-PSB) showed enhanced antifouling property and serum stability as seen by their nanoparticle size stability in the presence of serum and reduced red blood cell aggregation; the POSS-g-(PDMA-b-PSB) also somewhat retained its MIC in blood unlike the quaternized or random zwitterionic copolymers. The antibacterial kinetics study showed that Escherichia coli can be killed within 30 min by both random and block copolymers of POSS-g-(PDMA-co-PSB). Finally, our POSS star polymers showed low toxicity to zebrafish embryo and could be potentially used in aquaculture antibacterial applications.

Green Fabrication of Amphiphilic Quaternized β‐Chitin Derivatives with Excellent Biocompatibility and Antibacterial Activities for Wound Healing

“…[4b,7] Antimicrobial peptides have a low propensity for the development of resistance in bacteria; however, the clinical implementation of antimicrobial peptides has suffered from poor in vivo antimicrobial activity, salt instability, high cost, high hemolysis, and high toxicity. [7d,8] Inspired by the cationic charge and amphiphilic structure of antimicrobial peptides, numerous cationic polymers have been designed and synthesized, including polyacrylates, poly(ionic liquid)s,[5d,10] polycarbonates, and polynorbornenes . Some cationic polymer scaffolds are nonbiodegradable, and their preparation from monomers generally requires complicated chemical synthesis and purification processes involving organic solvents or toxic catalysts, which reduces their antimicrobial efficiency and biocompatibility .…”

Multifunctionalized Polyamides Prepared by Facile Ugi Reaction as Thermosensitive, Biocompatible and Antibacterial Biomaterials

“…The experiment indicated that compared with the control, PIA‐800, PBA‐800 and PFA‐800 without quaternary ammonium groups displayed no discernible discrepancy in the viability of E. coli and S. aureus after incubation for 24 h. However, the survival of the two bacteria decreased sharply when the concentration of PIA‐800‐Br, PBA‐800‐Br and PFA‐800‐Br was controlled at 1∼10 mg/mL. The results demonstrated that the antibacterial activity of three quaternized polyamides were theoretically derived from the cationic groups (N + ) on their chains, which was completely consistent with the previous reported research results …”

“…Therefore, the relatively more negative charges on S. aureus membrane enforces the electrostatic attraction with positively charged quaternary ammonium groups, which leads to the better antibacterial activity against S. aureus over E. coli . The results in our experiment were in complete agreement with the antibacterial activity of the reported polymers to against S. aureus over E. coli . Among the three quaternized polyamides, PFA‐800‐Br showed the best antibacterial activity, while PBA‐800‐Br presented the lowest antibacterial activity.…”

Biodegradable Antibacterial Polymeric Nanosystems: A New Hope to Cope with Multidrug‐Resistant Bacteria

“…Although antibiotic‐containing nanosystems significantly enhance antibacterial efficacy and slow down the emergences of multidrug resistant superbugs, the development of new materials with intrinsic antibacterial activities is still in urgent demand. Over the recent decades, the developments of polymers with intrinsic antimicrobial moieties, such as quaternary ammonium (QA) groups, phosphonium groups, AMPs and their synthetic mimics, have attracted striking attention in the field of biomaterials. In a pioneer work, a series of biodegradable triblock copolymers were synthesized via ring‐opening polymerization, containing two hydrophobic poly(trimethylene carbonate) (PTMC) blocks to form the core of micelles, and quaternized bactericidal blocks to form the shell of the micelles, as shown in Figure .…”