Antimicrobial Polymers Research Articles

Releasable antimicrobial polymer-silk coatings for combating multidrug-resistant bacteria

Controlled release of synthetic cationic antimicrobial polymers from silk-based coating for preventing bacterial biofilm formation on the surface and for killing planktonic bacteria cells.

Piperazine based antimicrobial polymers: a review.

Microbial infections are a life threatening concern in several areas, which include the biomedical sector, healthcare products, water purification systems, and food packaging. Polymers with low molecular weight bioactive agents or disinfectants help the scientific community to reduce the lethality rate caused by pathogenic microbes. Antimicrobial polymeric approach is one of the advanced approaches made by researchers in concern with the problems associated with small molecules that restrict their applications in broad spectrum. History reveals the synthesis of numerous antimicrobial polymers using various antimicrobial agents but lacks the use of piperazine molecule, which is of pharmaceutical importance. This review gives an insight into the current and future perspective for the development of piperazine-based antimicrobial polymers.

Influence of Chitosan Characteristics in the Microencapsulation of Essential Oils

The fight against nosocomial infections in hospitals, has promoted the use of microencapsulated essential oils on medical wearing uniforms. These types of microcapsules can be improved with the use of antimicrobial polymers in the shell structure. Chitosan is one of the most used biopolymers and the effectiveness of the treatment can be increased with the combination of different molecular weight chains of chitosan. This modification in the composition of shell structure allows controlling the rate of hydrolysis and, therefore the amount of its cationic form. The main objective of this work is to define a methodology to get microcapsules with different shell compositions, using surfactants as stabilizers in their first step. Once they have been obtained, these microcapsules will be fixed into textile substrates with the objective to use these tissues as surgical and medical clothes to spread the antibacterial effect, in sanitary staff, as well as in the own patient. In the process of microencapsulation the molecular weight distribution of polymers, influences strongly the delivery mechanisms of the active principle, as well as the chemical characteristics of the textile substrate used in every case. In this work, several chitosan biopolymers have been checked. Structural changes in the stabilization first step and the influence of the cross-linking extension have been related with the final antibacterial effect when fixed on cotton substrates.

Regulation of Lipid Bilayer Ion Permeability by Antibacterial Polymethyloxazoline-Polyethyleneimine Copolymers.

Amphiphilic antimicrobial polymers display activity against the outer bacterial cell membrane, triggering various physiological effects. We investigated the regulation of ion transport across the lipid bilayer to understand differences in biological activity for a series of amphiphilic polymethyloxazoline - polyethyleneimine copolymers. The results confirmed that the tested structures were able to increase the permeability of the lipid bilayer (LB) membrane or its rupture. Black lipid membrane (BLM) experiments show that the triggered conductance profile and its character is strongly correlated with the polymer structure and zeta potential. The polymer exhibiting the highest antimicrobial activity promotes ion transport by using a unique mechanism and step-like characteristics with well-defined discreet openings and closings. The molecule was incorporated into the membrane in a reproducible way, and the observed channel-like activity could be responsible for the antibacterial activity of this molecule.

Hot-melt extrusion of photodynamic antimicrobial polymers for prevention of microbial contamination

Infectious disease outbreaks within healthcare facilities can exacerbate patient illness and, in some cases, can be fatal. Contaminated surfaces and medical devices can act as a reservoir for transmission of pathogens and have been linked to the rising incidence of healthcare-acquired infections. Antimicrobial surfaces can reduce microbial contamination and transmission and have emerged as a crucial component in healthcare infection control in recent years. The aim of this study was to manufacture antimicrobial polymer surfaces containing the photosensitiser, toluidine blue O (TBO), using hot-melt extrusion (HME). Several concentrations of TBO were combined with a range of medically relevant polymers via HME. TBO-polymer extrudates displayed no significant differences in thermal properties and surface wettability relative to non-loaded polymers. Minimal leaching of TBO from the surface was confirmed through in vitro release studies. Antibacterial activity was observed to vary according to the polymer and concentration of incorporated TBO, with PEBAX® polymers modified with 0.1% w/w TBO demonstrating promising reductions of >99.9% in viable bacterial adherence of a range of common nosocomial pathogens, including Staphylococcus aureus, Staphylococcus epidermidis, Acinetobacter baumannii and Escherichia coli. This study demonstrates the use of HME as a facile alternative method to common encapsulation strategies for the production of light-activated antimicrobial polymer surfaces. This method can be easily translated to large-scale manufacture and, in addition, the polymers constitute promising antimicrobial base materials for the rapidly growing additive manufacturing industries.

A review on additive manufacturing of polymers composites

Additive Manufacturing, referred to as 3D printing has extended beyond simple prototyping and is being used for the fabrication of fully functional active components. It is one of the flexible manufacturing technique that can apply to polymers, metals, ceramics, concrete, and composites. Owing to the ability to select from a wide range of processible polymers and the enhancement in some of the properties offered by polymers, the AM industry, still predominantly targets the production of polymeric components. This review demonstrates the current state of AM industry regarding polymeric materials. A brief explanation of the additive manufacturing (AM) techniques, polymers, and polymer composites (fibre reinforces, particle reinforced and nanocomposites) utilised in the AM processes is provided. Polymer AM is being applied in different applications such as biomedical, electronics, aerospace, automobile, and sporting industries respectively. The review also emphasizes the rising importance of antimicrobial polymers in the COVID-19 pandemic. The exponential use of polymeric materials in the industrial sector has caused an increase in wastage generation and disposal issues which draws attention to the importance of green composites as well as life cycle assessment (LCA) of products and processes. Finally, the significance of Distributed Recycling via AM due to the disposal issues and low polymer recycling rates is illustrated.

Automation and data-driven design of polymer therapeutics.

Polymers are uniquely suited for drug delivery and biomaterial applications due to tunable structural parameters such as length, composition, architecture, and valency. To facilitate designs, researchers may explore combinatorial libraries in a high throughput fashion to correlate structure to function. However, traditional polymerization reactions including controlled living radical polymerization (CLRP) and ring-opening polymerization (ROP) require inert reaction conditions and extensive expertise to implement. With the advent of air-tolerance and automation, several polymerization techniques are now compatible with well plates and can be carried out at the benchtop, making high throughput synthesis and high throughput screening (HTS) possible. To avoid HTS pitfalls often described as "fishing expeditions," it is crucial to employ intelligent and big data approaches to maximize experimental efficiency. This is where the disruptive technologies of machine learning (ML) and artificial intelligence (AI) will likely play a role. In fact, ML and AI are already impacting small molecule drug discovery and showing signs of emerging in drug delivery. In this review, we present state-of-the-art research in drug delivery, gene delivery, antimicrobial polymers, and bioactive polymers alongside data-driven developments in drug design and organic synthesis. From this insight, important lessons are revealed for the polymer therapeutics community including the value of a closed loop design-build-test-learn workflow. This is an exciting time as researchers will gain the ability to fully explore the polymer structural landscape and establish quantitative structure-property relationships (QSPRs) with biological significance.

Antimicrobial Carbohydrate-Based Macromolecules: Their Structures and Activities.

Emerging drug resistance is creating an urgent demand for new antimicrobial therapeutics. Besides the development of conventional antibiotics, antimicrobial agents with novel mechanisms have attracted great attention, such as antimicrobial peptides and polymers. Interactions between carbohydrates and proteins on microbes are believed to be the first step of pathogenesis. Thus, considerable efforts have been made on the development of carbohydrate-containing molecules in antimicrobial research. Recent progress of glycosylated macromolecules for antimicrobial applications has been discussed with an emphasis on synthetic glycosylated materials.

Synergistic interactions of ionic liquids and antimicrobials improve drug efficacy.

SummaryCombinations of ionic liquids (ILs) with antimicrobial compounds have been shown to produce synergistic activities in model liposomes. In this study, imidazolium chloride-based ILs with alkyl tail length variations are combined with commercially available, small-molecule antimicrobials to examine the potential for combinatorial and synergistic antimicrobial effects on P. aeruginosa, E. coli, S. aureus, and S. cerevisiae. The effects of these treatments in a human cell culture model indicate the cytotoxic limits of ILs paired with antimicrobials. The analysis of these ILs demonstrates that the length of the alkyl chain on the IL molecule is proportional to both antimicrobial activity and cytotoxicity. Moreover, the ILs which exhibit synergy with small-molecule antibiotics appear to be acting in a membrane permeabilizing manner. Collectively, results from these experiments demonstrate an increase in antimicrobial efficacy with specific IL + antimicrobial combinations on microbial cultures while maintaining low cytotoxicity in a mammalian cell culture model.

Effect of Hydrophobic Groups on Antimicrobial and Hemolytic Activity: Developing a Predictive Tool for Ternary Antimicrobial Polymers.

Antimicrobial polymers have emerged as a potential solution to the growing problem of antimicrobial resistance. Although several studies have examined the effects of various parameters on the antimicrobial and hemolytic activity of statistical copolymers, there are still numerous parameters to be explored. Therefore, in this study, we developed a library of 36 statistical amphiphilic ternary copolymers prepared via photoinduced electron transfer-reversible addition-fragmentation chain transfer polymerization to systematically evaluate the influence of hydrophobic groups [number of carbons (5, 7, and 9)] and chain type of the hydrophobic monomer (cyclic, aromatic, linear, or branched), monomer ratio, and degree of polymerization (DPn) on antimicrobial and hemolytic activity. To guide our synthetic strategy, we developed a pre-experimental screening approach using C log P values of oligomer models, which correspond to the logarithm of the partition coefficient of compounds between n-octanol and water. This method enabled correlation of polymer hydrophobicity with antimicrobial and hemolytic activity. In addition, this study revealed that minimizing hydrophobicity and hydrophobic content were key factors in controlling hemolysis, whereas optimizing antimicrobial activity was more complex. High antimicrobial activity required hydrophobicity (i.e., C log P, hydrophobicity index) that was neither too high nor too low, an appropriate cationic/hydrophobic balance, and structural compatibility between the chosen monomers. Furthermore, these findings could guide the design of future antimicrobial ternary copolymers and suggest that C log P values between 0 and 2 have the best balance of high antimicrobial activity and low hemolytic activity.

The Mechanisms and the Applications of Antibacterial Polymers in Surface Modification on Medical Devices.

Medical device contamination caused by microbial pathogens such as bacteria and fungi has posed a severe threat to the patients’ health in hospitals. Due to the increasing resistance of pathogens to antibiotics, the efficacy of traditional antibiotics treatment is gradually decreasing for the infection treatment. Therefore, it is urgent to develop new antibacterial drugs to meet clinical or civilian needs. Antibacterial polymers have attracted the interests of researchers due to their unique bactericidal mechanism and excellent antibacterial effect. This article reviews the mechanism and advantages of antimicrobial polymers and the consideration for their translation. Their applications and advances in medical device surface coating were also reviewed. The information will provide a valuable reference to design and develop antibacterial devices that are resistant to pathogenic infections.

Novel LDPE/vermiculite/ciclopiroxolamine hybrid nanocomposites: Structure, surface properties, and antifungal activity

AbstractThe increasing number of indwelling medical materials and devices are connected with infections caused by yeast, especially Candida albicans. This pathogen produces biofilms on synthetic materials, which facilitates adhesion of the organisms to devices and renders them relatively refractory to medical therapy. Since antimicrobial polymer nanocomposites present one of the promising possibilities, this study explores a new approach to achieving this goal by developing nanocomposite based on low density polyethylene (LDPE) with clay mineral vermiculite as an active carrier for antifungal compound. The set of LDPE/clay nanocomposite with increasing amount of antifungal nanofiller was prepared by melt compounding procedure. As antifungal agent was selected generally used active substance ciclopiroxolamine and this compound was loaded into natural vermiculite through ultrasound technique. The structure of all prepared samples was studied by X‐ray diffraction analysis and Fourier transforms infrared spectroscopy. Further thermal properties of polyethylene/clay nanocomposites were investigated by thermogravimetric analysis and the surface properties were evaluated by light optical microscopy, scanning electron microscopy and atomic force microscopy. From mentioned characteristics, we conclude that presence of nanofiller in LDPE primarily causes shift of thermal degradation to higher temperatures and increasing of microhardness. All prepared LDPE nanocomposites possess an excellent and prolonged antifungal activity against Candida albicans.

Application of Antimicrobial Polymers in the Development of Dental Resin Composite

Dental resin composites have been widely used in a variety of direct and indirect dental restorations due to their aesthetic properties compared to amalgams and similar metals. Despite the fact that dental resin composites can contribute similar mechanical properties, they are more likely to have microbial accumulations leading to secondary caries. Therefore, the effective and long-lasting antimicrobial properties of dental resin composites are of great significance to their clinical applications. The approaches of ascribing antimicrobial properties to the resin composites may be divided into two types: The filler-type and the resin-type. In this review, the resin-type approaches were highlighted. Focusing on the antimicrobial polymers used in dental resin composites, their chemical structures, mechanical properties, antimicrobial effectiveness, releasing profile, and biocompatibility were included, and challenges, as well as future perspectives, were also discussed.

Antibacterial and hemolytic activity of cationic polymer-vancomycin conjugates

In this study, a Gram positive bacteria effective antibiotic, vancomycin (VAN), was conjugated with antimicrobial cationic polymers (ACPs) that were found to be active against both Gram positive and Gram negative bacteria previously, and the antibacterial activity of newly synthesized VAN-PEG-ACP conjugates were investigated. VAN was first PEGylated using Michael Addition method, then the ACPs, which were synthesized using ring-opening metathesis polymerization (ROMP), were bound covalently to the VAN-PEG structure using cross metathesis pathways and thus cationic polymer-vancomycin conjugates (VAN-PEG-ACPs) were obtained. The antimicrobial activity of the conjugates were investigated against Gram negative strain E. coli and Gram positive strains S. aureus and E. feacalis. Con_1_10k_1, Con_2a_3k_1, and Con_2b_3k_1 were found to be active towards S. aureus (MIC = 64 µg/ml, 32 µg/mL, and 32 µg/mL, respectively) and Con_2a_3k_1, and Con_2b_3k_1 were found to be active also towards E. feacalis (MIC = 16 µg/ml and 32 µg/mL, respectively), however they did not show activity towards E. coli. All the conjugates were found to be non-hemolytic towards red blood cells (HC50 = >1024 µg/mL). MTS assay results also showed that the conjugates did not lyse viable HUVEC cells within 72 h. The membrane deformation of S. aureus was monitored using scanning electron microscopy (SEM) techniques in the presence of the polymers and the conjugates.

An antimicrobial bio-based polymer foam from ZnO-stabilised pickering emulsion templated polymerisation

Pickering emulsion templating has become an effective method for preparing polymer foam with precise morphology. The present study reports an antibacterial foam prepared through the polymerisation of acrylated epoxidised soybean oil (AESO) in the external phase of a water-in-oil (w/o) Pickering emulsion. Zinc oxide (ZnO) was used to stabilise water into the AESO and endow the resulting foam with antimicrobial characteristics. The effects of the oil-to-water mass ratio (3:1–1:2) and ZnO concentration (0.1–3.0 wt%) on the stability of the emulsion were studied. The emulsions were characterised in terms of the volume fraction of the emulsion phase, the viscosity of the emulsion, and the interfacial tension. The emulsion prepared with an oil-to-water ratio of 3:2 and ZnO concentration of 1.0 wt% showed strong stability. Absorption of ZnO at the oil–water interface was observed by using graphene oxide quantum dot-doped ZnO as a fluorescent marker. Antibacterial foam was formed by heating the Pickering emulsion at 120 °C for 3 h. Scanning electron microscope images show that the foam has a closed-cell structure with an average pore diameter of approximately 200 μm. The prepared foam showed antibacterial activity with an inhibition rate against E.coli of 99%. The production of a porous polymer from sustainable materials through ZnO-stabilised Pickering emulsion templating provides a facile method for preparing innovative, functional bio-based materials.

Fabrication of 3D printed antimicrobial polycaprolactone scaffolds for tissue engineering applications

Synthetic polymers are widely employed for bone tissue engineering due to their tunable physical properties and biocompatibility. Inherently, most of these polymers display poor antimicrobial properties. Infection at the site of implantation is a major cause for failure or delay in bone healing process and the development of antimicrobial polymers is highly desired. In this study, silver nanoparticles (AgNps) were synthesized in polycaprolactone (PCL) solution by in-situ reduction and further extruded into PCL/AgNps filaments. Customized 3D structures were fabricated using the PCL/AgNps filaments through 3D printing technique. As demonstrated by scanning electron microscopy, the 3D printed scaffolds exhibited interconnected porous structures. Furthermore, X-ray photoelectron spectroscopy analysis revealed the reduction of silver ions. Transmission electron microscopy along with energy-dispersive X-ray spectroscopy analysis confirmed the formation of silver nanoparticles throughout the PCL matrix. In vitro enzymatic degradation studies showed that the PCL/AgNps scaffolds displayed 80% degradation in 20 days. The scaffolds were cytocompatible, as assessed using hFOB cells and their antibacterial activity was demonstrated on Escherichia coli. Due to their interconnected porous structure, mechanical and antibacterial properties, these cytocompatible multifunctional 3D printed PCL/AgNps scaffolds appear highly suitable for bone tissue engineering.

Polymeric ruthenium precursor as a photoactivated antimicrobial agent

Ruthenium coordination compounds have demonstrated a promising anticancer and antibacterial activity, but their poor water solubility and low stability under physiological conditions may limit their therapeutic applications. Physical encapsulation or covalent conjugation with polymers may overcome these drawbacks, but generally involve multistep reactions and purification processes. In this work, the antibacterial activity of the polymeric precursor dicarbonyldichlororuthenium (II) [Ru(CO)2Cl2]n has been studied against Escherichia coli and Staphylococcus aureus. This Ru-carbonyl precursor shows minimum inhibitory concentration at nanogram per millilitre, which renders it a novel antimicrobial polymer without any organic ligands. Besides, [Ru(CO)2Cl2]n antimicrobial activity is markedly boosted under photoirradiation, which can be ascribed to the enhanced generation of reactive oxygen species under UV irradiation. [Ru(CO)2Cl2]n has been able to inhibit bacterial growth via the disruption of bacterial membranes and triggering upregulation of stress responses as shown in microscopic measurements. The activity of polymeric ruthenium as an antibacterial material is significant even at 6.6 ng/mL while remaining biocompatible to the mammalian cells at much higher concentrations. This study proves that this simple precursor, [Ru(CO)2Cl2]n, can be used as an antimicrobial compound with high activity and a low toxicity profile in the context of need for new antimicrobial agents to fight bacterial infections.

Determination of Pharmacokinetic Parameters of a Four-Armed, Guanidinium-Rich Structurally Nanoengineered Antimicrobial Peptide Polymer: A Research Protocol

Introduction: Antibacterial resistance has accentuated the need for the development of novel, efficacious pharmaceuticals. Structurally nanoengineered antimicrobial polypeptide polymers (SNAPPs) have shown promise as a candidate for a new antibacterial pharmaceutical class which may help overcome the problem of antibacterial resistance in humans or animals. Particularly, the SNAPP with a chemical formula (RGRGRGRGRGRG)4K2K-NH2 (4R6G6) has been shown to exhibit negligible hemolysis while retaining low minimal inhibitory concentrations against bacteria. An important consideration in drug development is pharmacokinetic studies, however, there have been no prior pharmacokinetic studies involving SNAPPs. Therefore, the objective of this study is to determine the pharmacokinetic parameters of 4R6G6. Methods: 4R6G6 will be synthesized and purified according to previously reported methods. 4R6G6 will be administered to BALB/c mice intravenously, serial blood samples will be taken from 0-48 hours after SNAPP administration and serum 4R6G6 concentrations will be quantified over time by liquid chromatography mass spectrometry. This information will be used to calculate key pharmacokinetic parameters using Pmetrics. Results: We expect that the half-life of elimination will be on the order of hours and will exceed 3 hours, while the volume of distribution will be equal to the plasma volume of a mouse (1.2 mL/mouse) Discussion: The half-life of elimination of 4R6G6 will influence its desirability as a future drug target. Additionally, the volume of distribution is expected to indicate a distribution into plasma, and can be used to calculate the desired dose for a certain plasma concentration in future studies. Conclusion: Given the expected half-life of elimination on the order of hours, we expect 4R6G6 to be a strong candidate for further translational study in the race to combat antibacterial resistance. Future directions include the quantification of the safety of the drug by determining the therapeutic index in vivo.

Guanidinylated Amphiphilic Polycarbonates with Enhanced Antimicrobial Activity by Extending the Length of the Spacer Arm and Micelle Self‐Assembly

Front Cover: The authors conducted research on antimicrobial polymer structure-activity relationships (SARs) based on their platform of guanidine containing aliphatic biodegradable polycarbonates with varying amphiphilicity and charge densities. These guanidinylated polycarbonates exhibited potent antimicrobial activity, but with low hemolytic activity. Furthermore, these polymers exhibited the ability to self-assemble and present micelle-like nanostructure due to their intrinsic amphiphilic macromolecular structure. This cover art depicts the antimicrobial polymer strands and their aggregation as nanoparticles in an aqueous environment, and the polymer micelles contacting the microbes in suspension, causing the membrane disruption that is the basis of the antimicrobial properties. This is reported by Chloe A. Cho, Chao Liang, Janesha Perera, Margaret A. Brimble, Simon Swift, Jianyong Jin in article 2000065.

STRUCTURE-ACTIVITY RELATIONSHIPS AND SURFACE IMMOBILIZATION OF POLYCATIONIC ANTIMICROBIALS

Antimicrobial agents have been the subject of scientific interest for the last few decades. However, the emergence of a novel coronavirus and pandemic that ensued has brought a new sense of urgency to the field of antibacterial research. The most urgent needs to mitigate the pandemic are self-disinfecting health equipment and antimicrobial protective equipment such as gowns for healthcare workers and face masks for the general public. At a time of high demand for antimicrobial products, understanding the mechanisms involved in antimicrobial polymers will be a benefit. In this review, the definition of antimicrobials and their classification according to the mode of action, as well as their chemical structure, were explained and used to build the fundamental understanding about antimicrobials and the working principles behind their action. The discussion continued with factors that affect the antimicrobial activity, which is the focus of the review. The first part of the review deals with free antimicrobial polymers in solution. The effect of molecular weight, counterions, spacer length and alkyl chain to the efficacy of antimicrobial polymers are highlighted and discussed at length. Focus in the second part shifts towards surface-immobilized antimicrobial polymers and their methods of immobilization.