274777 A Nonfouling Zwitterionic Polymer with Built-in Antimicrobial Functions
Bacterial surface adhesion and subsequent colonization have been among major issues plaguing the application of many biomedical devices, causing device failure as well as tissue infections. Traditionally, two common approaches exist to combat such threats. The first approach utilizes antimicrobial agents, particularly quaternary ammonium compounds and small molecular weight antibiotics, to actively kill the bacteria. The second approach uses nonfouling coatings such as poly (ethylene glycol) (PEG) and zwitterionic materials to fend off bacteria from adhering onto the surface. Despite their popularity, each has its own significant drawbacks. In recent years, we have reported several approaches to integrate antimicrobial and nonfouling strategies into one coating by switching between the cationic antimicrobial form and the zwitterionic nonfouling form. However, for all of these approaches, it inevitably involves a positively charged state at the bactericidal stage of their action. Such cationic materials are subject to severe biofouling, thus making them unsuitable for many applications where these materials are in constant contact with the complex media. Ideally, one could integrate the biological functionality, antimicrobial activity in this case, and “stealth” property into one single molecule thus keeping the surface free from bacteria while inhibiting bulk bacterial growth in a controllable manner under biological environments.
In this work, we report the design, synthesis and characterization of a new polymer that will meet the criteria and provide the capabilities aforementioned. In this system, poly PCBSA polymers consist of an antimicrobial leaving group salicylic acid (SA) conjugated to a carboxyl betaine (CB) zwitterionic unit through a hydrolysable ester linkage. This drug conjugation enjoys a high drug loading capacity unattainable via post-polymerization modification and a controlled drug release rate. More importantly, this resulting functional polymer maintains its zwitterionic state and nonfouling property all the time before and after the SA release, thus keeping the surface free from bacteria and inhibiting bacterial growth in bulk. Our study shows that the PCBSA polymer has a nonfouling property comparable to that of the benchmark zwitterionic nonfouling polymer PCBMA-2 at both the protein and bacterial levels. Additionally, PCBMA polymers were also proven to effectively inhibit bacteria proliferation in the surrounding environment through controlled release of small molecular weight antimicrobial agent.