Synthetic Polymer Mimics Antimicrobial Properties of Host-Defense Proteins

Author: 
Bob Michaels
Scanning electron microscopy images show how PolyMedix’s synthetic polymer antimicrobial agents disrupt the membrane of E. coli bacteria.

Bacterial infections caused by medical implants afflict tens of thousands of patients and result in upwards of 24,000 deaths each year in the United States. While silver has emerged as the antimicrobial material of choice, the precious metal also has its detractors. Among them is PolyMedix (Radnor, PA), which is developing a family of synthetic polymer antimicrobial agents that mimics the natural defenses of the human body.

The company’s PolyCide family of antimicrobial materials is active against hundreds of Gram-positive and Gram-negative drug-resistant bacteria and 399 kinds of staph bacteria, says Nicholas Landekic, PolyMedix’s president, CEO, director, and founder. Consisting of fully synthetic compounds made from commercially available starting materials, the family includes three classes of agents: one-step methacrylate polymers synthesized from two commercially available prepolymers, two- or three-step polynorbornenes, and five-step phenylalkyne oligomers.

These materials mimic natural host-defense proteins, Landekic explains. Produced in all higher forms of life, host-defense proteins such as magainins and cecropins protect against bacterial infections. In humans, this role is played by defensins, amphiphilic peptides featuring both a hydrophobic and a spatially opposing hydrophilic face that can act selectively on bacterial cell membranes. It is this property that the PolyCide materials have been designed to mimic.

“Like host-defense proteins, the PolyCides can form pores in the outer layer of bacterial membranes, causing bacterial cell death by direct biophysical membrane disruption,” Landekic says. “This process of direct membrane lysis is fundamentally different from most other antimicrobial mechanisms, which are biochemical in nature.” This biophysical mechanism, he adds, reduces the likelihood of bacterial resistance.

The PolyCides are water soluble and heat stable to approximately 200°C. They can also be incorporated into materials by injection molding, extrusion, or solvent melt-casting processes. Capable of being mixed into a variety of materials—including PVC, polyurethane, silicone, PLGA, styrene, polysulfone, and polyester—the antimicrobials can either be incorporated into the substrate of the device structure itself or applied as a coating in a PVC, polyurethane, or similar carrier. “As long as the surface is accessible to the PolyCide polymer, the material can exert its antimicrobial activity,” Landekic says.

Besides having different structures and mechanisms, silver-based antimicrobial agents and the PolyCide materials differ in several other respects. For example, while silver compounds require approximately 24 hours to kill bacteria, the PolyCides can accomplish this task in less than one minute, Landekic states. He adds that while silver acts poorly on biofilms, the PolyCides act rapidly in both disrupting existing biofilms and in preventing the formation of new ones. And while silver compounds must leach into the bacterial cell, the PolyCides act on the cell surface. Finally, silver ions exhibit cytotoxicity that accumulates in body tissue. In contrast, the PolyCides are highly selective toward bacterial versus human cells, according to Landekic.

“Many types of medical devices—such as surgical sutures, catheters, intravenous tubing, implantable joints, bandages, and wound dressings—could benefit from our antimicrobial material,” Landekic says. Like host-defense proteins, which have developed resistance to bacteria over hundreds of millions of years, the PolyCides offer broad resistance against bacteria, as evidenced by 18 sets of serial passage experiments and single-point mutation assays. Landekic concludes, “PolyMedix has thus learned from nature to mimic one of the oldest and most effective immune system defenses against bacterial infection.”