Suppressing Antibacterial Resistance: Chemical Binding of Monolayer Quaternary Ammonium Salts to Polymethyl Methacrylate in an Aqueous Solution and Its Clinical Efficacy

Lee Lee,Chang Chang,Chen Chen

doi:10.3390/ijms20194668

Abstract

Antibacterial resistance (ABR) poses an enormous threat to human health. ABR mainly develops due to bacteria being constantly exposed to diluted levels of disinfectants. Here, we propose a method for suppressing ABR through the chemical binding of disinfectants to polymethyl methacrylate (PMMA) device surfaces in solutions of 5%, 10%, and 20% disinfectant concentrations. PMMA discs were fabricated from a commercial orthodontic acrylic resin system (Ortho-Jet) and quaternary ammonium salts (QAS), 3-(trimethoxysilyl)-propyldimethyloctadecyl ammonium chloride (42% in methanol), were used as the disinfectant. The PMMA surfaces were activated in 3 M sulfuric acid at 80 °C for 5 h for the esterification of hydrolyzed QAS to PMMA. Fourier transform infrared difference spectra confirmed that the carboxy-terminated PMMA was chemically bound to the QAS. In vitro cell viability tests using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assays revealed that 5%QAS-c-PMMA was more biocompatible than 10%QAS-c-PMMA and 20%QAS-c-PMMA. The results of antibacterial tests and clinical trials demonstrated the excellent antibacterial power of 5%QAS-c-PMMA. This method is the first solution-based approach to successfully avoid disinfectant leakage and subsequent ABR, as revealed by mass spectrometry studies of the solution obtained by agitating the disinfectant-bound PMMA for 28 days.

Highlights

The evolution of antibacterial resistance (ABR) in bacterial pathogens [1,2] and the emergence of antibiotic-resistant bacterial strains [3] have caused increasingly severe threats to global public health [4,5]
Polymethyl methacrylate (PMMA) and its composites are the predominant biomaterials used for indwelling devices, which are loaded with antibiotics or disinfectants as a standard procedure for antibacterial treatment [11,12]
They include (1) the swelling penetration of Ag or Au nanoparticles by pouring a tetrahydrofuran solution onto PMMA films [19]; (2) atomic layer deposition of ZnO films on PMMA substrates using diethylzinc and water precursors [20]; (3) stirring grafting of Ag nanoparticles encapsulated with polymers with surface functional groups to PMMA supports [2]; (4) deposition of chitosan-stabilized disinfectant nanoparticles on PMMA using a heterocoagulation technique [21]; (5) repeated dip-coating of PMMA slides with dendritic porous nanostructures embedded with disinfectant nanoparticles before organic vapor treatment [22]; and (6) plasma activation of PMMA surfaces with subsequent immersion of the activated samples into a disinfectant solution [23,24]

Summary

Introduction

The evolution of antibacterial resistance (ABR) in bacterial pathogens [1,2] and the emergence of antibiotic-resistant bacterial strains [3] have caused increasingly severe threats to global public health [4,5]. To reduce the release of loaded disinfectants from the processed PMMA and the subsequent development of antimicrobial resistance, different approaches have been reported for grafting antibiotics to PMMA surfaces They include (1) the swelling penetration of Ag or Au nanoparticles by pouring a tetrahydrofuran solution onto PMMA films [19]; (2) atomic layer deposition of ZnO films on PMMA substrates using diethylzinc and water precursors [20]; (3) stirring grafting of Ag nanoparticles encapsulated with polymers with surface functional groups to PMMA supports [2]; (4) deposition of chitosan-stabilized disinfectant nanoparticles on PMMA using a heterocoagulation technique [21]; (5) repeated dip-coating of PMMA slides with dendritic porous nanostructures embedded with disinfectant nanoparticles before organic vapor treatment [22]; and (6) plasma activation of PMMA surfaces with subsequent immersion of the activated samples into a disinfectant solution [23,24]. The transfer of encoded plasmids arising from the omnipresence of diverse antibacterial agents resulting from overuse may promote the spread of multi-drug-resistant plasmids [33]

Methods

Findings

Discussion

Conclusion