Antimicrobial polymer

Antimicrobial polymers, also known as polymeric biocides, is a class of polymers with antimicrobial activity, or the ability to inhibit the growth of microorganisms such as bacteria, fungi or protozoans. These polymers have been engineered to mimic antimicrobial peptides which are used by the immune systems of living things to kill bacteria. Typically, antimicrobial polymers are produced by attaching or inserting an active antimicrobial agent onto a polymer backbone via an alkyl or acetyl linker. Antimicrobial polymers may enhance the efficiency and selectivity of currently used antimicrobial agents, while decreasing associated environmental hazards because antimicrobial polymers are generally nonvolatile and chemically stable. This makes this material a prime candidate for use in areas of medicine as a means to fight infection, in the food industry to prevent bacterial contamination, and in water sanitation to inhibit the growth of microorganisms in drinking water. Antimicrobial polymers, also known as polymeric biocides, is a class of polymers with antimicrobial activity, or the ability to inhibit the growth of microorganisms such as bacteria, fungi or protozoans. These polymers have been engineered to mimic antimicrobial peptides which are used by the immune systems of living things to kill bacteria. Typically, antimicrobial polymers are produced by attaching or inserting an active antimicrobial agent onto a polymer backbone via an alkyl or acetyl linker. Antimicrobial polymers may enhance the efficiency and selectivity of currently used antimicrobial agents, while decreasing associated environmental hazards because antimicrobial polymers are generally nonvolatile and chemically stable. This makes this material a prime candidate for use in areas of medicine as a means to fight infection, in the food industry to prevent bacterial contamination, and in water sanitation to inhibit the growth of microorganisms in drinking water. Antimicrobial agents kill bacteria through different methods depending on the type of bacteria. Most antiseptics and disinfectants kill bacteria immediately on contact by causing the bacterial cell to burst, or by depleting the bacteria's source of food preventing bacterial reproduction, also known as bacterial conjugation. Antimicrobial polymers commonly kill bacteria through this first method, which is accomplished through a series of steps, shown in Figure 1. First, the polymer must adsorb onto the bacterial cell wall. Most bacterial surfaces are negatively charged, therefore the adsorption of polymeric cations has proved to be more effective than adsorption of polymeric anions. The antimicrobial agent must then diffuse through the cell wall and adsorb onto the cytoplasmic membrane. Small molecule antimicrobial agents excel at the diffusion step due to their low molecular weight, while adsorption is better achieved by antimicrobial polymers. The disruption of the cytoplasmic membrane and subsequent leakage of cytoplasmic constituents leads to the death of the cell. Comparison of small molecule antimicrobial agents and antimicrobial polymers are shown in the following table: The molecular weight of the polymer is perhaps one of the most important properties to consider when determining antimicrobial properties because antimicrobial activity is markedly dependent on the molecular weight. It has been determined that optimal activity is achieved when polymers have a molecular weight in the range of 1.4x104 Da to 9.4x104 Da. Weights larger than this range show a decrease in activity. This dependence on weight can be attributed to the sequence of steps necessary for biocidal action. Extremely large molecular weight polymers will have trouble diffusing through the bacterial cell wall and cytoplasm. Thus much effort has been directed towards controlling the molecular weight of the polymer. Most bacterial cell walls are negatively charged, therefore most antimicrobial polymers must be positively charged to facilitate the adsorption process. The structure of the counter ion, or the ion associated with the polymer to balance charge, also affects the antimicrobial activity. Counter anions that form a strong ion-pair with the polymer impede the antimicrobial activity because the counter ion will prevent the polymer from interacting with the bacteria. However, ions that form a loose ion-pair or readily dissociate from the polymer, exhibit a positive influence on the activity because it allows the polymer to interact freely with the bacteria. The spacer length or alkyl chain length refers to the length of the carbon chain that composes the polymer backbone. The length of this chain has been investigated to see if it affects the antimicrobial activity of the polymer. Results have generally shown that longer alkyl chains have resulted in higher activity. There are two primary explanations for this effect. Firstly, longer chains have more active sites available for adsorption with the bacteria cell wall and cytoplasmic membrane. Secondly, longer chains aggregate differently than shorter chains, which again may provide a better means for adsorption. However, shorter chain lengths diffuse more easily. A major disadvantage of antimicrobial polymers is that macromolecules are very large and thus may not act as fast as small molecule agents. Biocidal polymers that require contact times on the order of hours to provide substantial reductions in pathogens, really have no practical value. Seconds, or minutes at most, should be the contact time goal for a real application. Furthermore, if the structural modification to the polymer caused by biocidal functionalization adversely affects the intended use, the polymer will be of no practical value. For example, if a fiber that must be exposed to aqueous bleach to render it antimicrobial (an N-halamine polymer) is weakened by that exposure, or its dye is bleached, it will have limited use. This synthetic method involves covalently linking antimicrobial agents that contain functional groups with high antimicrobial activity, such as hydroxyl, carboxyl, or amino groups to a variety of polymerizable derivatives, or monomers before polymerization. The antimicrobial activity of the active agent may be either reduced or enhanced by polymerization. This depends on how the agent kills bacteria, either by depleting the bacterial food supply or through bacterial membrane disruption and the kind of monomer used. Differences have been reported when homo-polymers are compared to copolymers. Examples of antimicrobial polymers synthesized from antimicrobial monomers are included in Table 2: Table 2: Polymers Synthesized from Antimicrobial Monomers and their Antimicrobial Properties This synthetic method involves first synthesizing the polymer, followed by modification with an active species. The following kinds of monomers are usually used to form the backbone of homopolymers or copolymers: vinylbenzyl chloride, methyl methacrylate, 2-chloroethyl vinyl ether, vinyl alcohol, maleic anhydride. The polymers are then activated by anchoring antimicrobial species, such as phosphonium salts, ammonium salts, or phenol groups via quaternization, substitution of chloride, or hydrolysis of anhydride. Examples of polymers synthesized from this method are provided in Table 3: