Polymers with the ability to kill or inhibit the growth of microorganisms such as bacteria, fungi, or viruses are classified as antimicrobial agents. This class of polymers consists of natural polymers with inherent antimicrobial activity and polymers modified to exhibit antimicrobial activity. Polymers are generally nonvolatile, chemically stable, and can be chemically and physically modified to display desired characteristics and antimicrobial activity. Antimicrobial polymers are a prime candidate for use in the food industry to prevent bacterial contamination and in water sanitation to inhibit the growth of microorganisms in drinking water.
Mechanism of action Antimicrobial polymers inhibit cell growth and initiate cell death through two primary mechanisms. The first mechanism is utilized by contact-active polymers. Contact-active polymers utilize electrostatic interactions, the hydrophobic effect, and the chelate effect. Electrostatic attraction is a common initial interaction of an antimicrobial polymer with a microbe. The chelating and hydrophobic effects are common secondary interactions of antimicrobial polymers with microbes.
Cationically charged antimicrobial polymers are attracted to the anionically charged bacterial cell walls. The outer wall of bacterial cells possesses a net negative charge. The cytoplasmic membrane of bacterial cells has a negative charge and contains essential proteins. The secondary interaction, the chelating effect, involves the bonding of the antimicrobial polymer to the microbial cell. These interactions lead to membrane disruption and ultimately inhibited cell growth or death.
The cytoplasmic membrane of a cell is a semi-permeable membrane, which controls the transport of solutes into the cell. The phospholipid bilayer is an important component of the cell membrane, which is composed of hydrophilic heads and a hydrophobic tail. The hydrophilic heads form the inner and outer linings of the cell membrane, while the hydrophobic tails compose the interior of the membrane. The secondary interaction, the hydrophobic effect, involves the accumulation of nonpolar compounds away from water. Nonpolar components of antimicrobial polymers insert themselves into the nonpolar interior of the cell membrane.
High molecular weight polymers commonly induce cell death or inhibition through contact-active interactions with the surface of cells. Cell death and inhibition result from impairment of normal cellular function. Positive residues on the polymer electrostatically interact with negative charges on the cell and induce secondary cellular effects. Cellular membrane penetration is common in low molecular weight polymers. The initial electrostatic and hydrophobic interaction of an antimicrobial polymer and biomimetic polymer causes membrane disruption and cell death. The hydrophobic tail of the polymer penetrates the phospholipid bilayer into the hydrophobic region, resulting in membrane disruption and denaturing of proteins and enzymes, as well as other secondary effects. Secondary effects include disruption of solute and electron transport as well as disturbances to energy production pathways, which leads to cell death.
The second mechanism is characterized by the release of low molecular weight antimicrobial agents from polymers. Antimicrobial agents that are released from polymers induce cell death through binding to or penetrating the cell wall. When antimicrobial agents bind to proteins, structural changes occur to the cell membrane, resulting in cellular death. The penetration of nanoparticle antimicrobial agents into the cell wall enables the antimicrobial agents to interact with cell DNA. Microbe death results from the effects to DNA transcription and mRNA synthesis when polymer nanoparticles combine with DNA.
Primary characteristics of antimicrobial polymers There are different primary characteristics of antimicrobial polymers, dependent upon the mechanism of action. The two primary characteristics of contact-active antimicrobial polymers are cationic charge and hydrophobicity. Cationic residues are necessary to induce the interaction with the microbial cell wall. Polycations such as quaternary ammonium, quaternary phosphonium, and guanidinium are frequently found in antimicrobial polymers. Hydrophobic residues improve binding to the lipid bilayer and are utilized for insertion into the microbial cell wall. Non-contact-active antimicrobial polymers require the addition of antimicrobial agents to induce activity. Common agents added include N-halamine compounds, nitric oxide, and copper and silver nanoparticles.
Classes of antimicrobial polymers Antimicrobial polymers are generally classified into two categories based on how antimicrobial activity is conferred. The first are polymers with inherent antimicrobial effects which do not require any modifications to incite antimicrobial behavior. The other class requires modification to enable antimicrobial activity and can be differentiated by the type of modification. Polymers may be chemically modified to induce antimicrobial behavior or they may be used as a backbone for the addition of organic or inorganic compounds.
Inherent antimicrobial activity Polymers with inherent antimicrobial activity include chitosan, poly-ε-lysine, quaternary ammonium compounds, polyethylenimine, and polyguanidines. Chitosan is a nontoxic polymer that has displayed broad-spectrum antimicrobial activity. The mechanism of action for chitosan includes electrostatic interaction, the chelate effect, and the hydrophobic effect. Electrostatic interaction is the primary initial interaction when the pH is lower, while the chelating and hydrophobic effects are the primary initial interactions when the pH is higher. Growth inhibition and death of fungi, bacteria, and yeasts have been seen from chitosan. The antimicrobial effect of chitosan is greater on fungi than yeasts and more effective on gram-negative bacteria than gram-positive bacteria.
Poly-ε-lysine is a biodegradable, nontoxic, edible antimicrobial polymer. This polymer utilizes electrostatic interactions to attach to the cell wall, therefore disrupting the integrity of the cell wall. Poly-ε-lysine penetrates the cell wall, causing physiological damage to the cell and death. In comparison to a similar synthetic polymer, poly-ε-lysine is more effective against gram-positive than gram-negative bacteria. Poly-ε-lysine is also effective against Bacillus coagulans, Bacillus stearothermophilus, and Bacillus subtilis.
Benzalkonium chloride, stearalkonium chloride, and cetrimonium are all quaternary ammonium compounds containing nitrogen. The antibacterial activity of these compounds is affected by the number of carbon atoms and the length of the nitrogen-containing chain. Optimal antimicrobial activity is generally seen in quaternary ammonium compounds with a long chain length, containing 8 to 18 carbon atoms. Increased activity is seen against gram-positive bacteria in polymers with a chain length of 12 to 14 carbon atoms, while improved activity against gram-negative bacteria is seen in polymers with a chain length of 14 to 16 carbon atoms. Polymer quaternary ammonium compounds containing nitrogen induce cell death through electrostatic interactions and the hydrophobic effect. This group of polymers displays limited hemolytic activity, making them advantageous for use in cosmetics and healthcare.
Polyethylenimine is a synthetic, nonbiodegradable polymer containing nitrogen. This polymer induces cell death through cell membrane rupture. When attached to immobilized surfaces including glass and plastic, N-alkyl-polyethylenimine caused cell inactivation in almost 100% of airborne and waterborne bacteria and fungi. A benefit of this polymer is that it is nontoxic to mammalian cells. Polyethylenimine has been applied in the medical industry for use in prostheses. Bacteria growth was reduced by 92% when polyethylenimine was tested as a coating surface for medical devices. The activity of polyethylenimine is affected by the molecular weight of the polymer; low molecular weight polyethylenimine displays negligible activity, while displaying great antimicrobial activity in its high molecular weight form.
Polyguanidines are another class of antimicrobial polymers containing nitrogen. This class of antimicrobial polymers is nontoxic and exhibits high water solubility. Polyguanidines display broad-spectrum antimicrobial activity and initially interact with microbes using electrostatic forces. Greater activity against gram-positive bacteria has been seen with polyguanidines than against gram-negative bacteria. The reason for the difference in activity is likened to the different structures of gram-positive and gram-negative bacteria. Gram-negative bacteria have a thinner peptidoglycan layer than gram-positive bacteria. In addition, gram-negative bacteria have an outer lipid membrane, while gram-positive bacteria do not. High molecular weight polymers are able to penetrate gram-positive bacteria.
Antimicrobial activity through chemical modification This class of polymers does not have any inherent antimicrobial activity. To induce antimicrobial activity, polymers are chemically modified to include active agents. Active side groups are attached to the polymer backbone to generate antimicrobial activity. Pendant groups, antibiotic drugs, or inorganic particles can be adjoined to the polymer.
Pendant groups that are attached to the polymer backbone include quaternary ammonium, hydroxyl groups with an organic acid, and others. Antimicrobial polymers containing quaternary ammonium as a side group are commonly synthesized from methacrylic monomers. The benefit of these monomers is that the hydrophobicity, molecular weight, and surface charge can all be manipulated. Hydrophobicity of the polymer has a strong effect on antimicrobial activity. Polysiloxanes, which have a quaternary ammonium pendant group, have demonstrated activity against several strains of bacteria including Enterococcus hirae, E. coli, and P. aeruginosa. The flexibility and amphiphilic nature of this polymer enhances the antimicrobial activity. When benzaldehyde, a hydroxyl group containing organic acid, is used as a side group with methyl methacrylate polymers, growth inhibition five times that of control surfaces has been shown. Benzaldehyde has inherent antimicrobial activity and has been incorporated into polymers to improve activity. Polymers with quaternary ammonium or hydroxyl groups with an organic acid as a pendant group have demonstrated activity against many types of bacteria, fungi, and algae.