Global health is increasingly being threatened by the rapid emergence of drug-resistant microbes. The ability of these microbes to form biofilms has further exacerbated the scenario leading to notorious infections that are almost impossible to treat. For addressing this clinical threat, various antimicrobial polymers, polymer-based antimicrobial hydrogels and polymer-coated antimicrobial surfaces have been developed in the recent past. This review aims to discuss such polymer-based antimicrobial strategies with a focus on their current advancement in the field. Antimicrobial polymers, whose designs are inspired from antimicrobial peptides (AMPs), are described with an emphasis on structure-activity analysis. Additionally, antibiofilm activity and in vivo efficacy are delineated to elucidate the real potential of these antimicrobial polymers as possible therapeutics. Antimicrobial hydrogels, prepared from either inherently antimicrobial polymers or biocide-loaded into polymer-derived hydrogel matrix, are elaborated followed by various strategies to engineer polymer-coated antimicrobial surfaces. In the end, the current challenges are accentuated along with future directions for further expansion of the field toward tackling infections and antimicrobial resistance.

Preventing bacterial biofilm formation on medical devices and implants in vivo still remains a daunting task. Current antibacterial coatings to combat implant-associated infections are generally composed of toxic metals or nondegradable polymers and involve multistep surface modifications. Here, we present a charge-switchable antibacterial and antibiofilm coating based on water-insoluble cationic hydrophobic polymers that are soluble in organic solvents and can be noncovalently coated onto different surfaces. Toward this, a library of quaternary polyethylenimine (QPEI) polymers with an amide or ester group in their pendant alkyl chain was developed. These QPEIs are shown to hydrolyze from active cationic to nontoxic zwitterionic polymers under acidic or enzymatic conditions. Notably, polymers with both zwitterionic and cationic groups, obtained upon partial hydrolysis of QPEIs, are shown to retain their antibacterial activity with much lower toxicity toward mammalian cells. Furthermore, the zwitterionic polymer, a fully hydrolyzed product of the QPEIs, is shown to be nontoxic to mammalian cells in vitro as well as in vivo. The QPEIs, when coated onto surfaces, kill bacteria and prevent formation of biofilms. In an in vivo mice model, the QPEI-coated medical grade catheter is shown to reduce methicillin-resistant Staphylococcus aureus contamination both on the catheter surface and in the adjacent tissues (99.99% reduction compared to a noncoated catheter). Additionally, biofilm formation is inhibited on the catheter surface with negligible inflammation in the adjacent tissue. The above results thus highlight the importance of these polymers to be used as effective antibacterial coatings in biomedical applications.

Microbial attachment and subsequent colonization onto surfaces lead to the spread of deadly community-acquired and hospital-acquired (nosocomial) infections. Cationic polymeric coatings have gained enormous attention to tackle this scenario. However, non-biodegradable cationic polymer coated surfaces suffer from accumulation of microbial debris leading to toxicity and consequent complexities. Synthetic reproducibility and sophisticated coating techniques further limit their application. In this present study, we have developed one-step curable, covalent coatings based on two organo- and water-soluble small molecules, quaternary benzophenone-based ester and quaternary benzophenone-based amide, which can cross-link on surfaces upon UV irradiation. Upon contact, the coating completely killed bacteria and fungi in vitro including drug-resistant pathogens methicillin-resistant Staphylococcus aureus (MRSA) and fluconazole-resistant Candida albicans spp. The coating also showed antiviral activity against notorious influenza virus with 100% killing. The coated surfaces also killed stationary-phase cells of MRSA, which cannot be eradicated by traditional antibiotics. Upon hydrolysis, the surfaces switched to an antifouling state displaying significant reduction in bacterial adherence. To the best of our knowledge, this is the first report of an antimicrobial coating which could kill all of bacteria, fungi, and influenza virus. Taken together, the antimicrobial coating reported herein holds great promise to be developed for further application in healthcare settings.

The rapid growth of antibiotic resistance in Staphylococcus aureus coupled with their biofilm forming ability has made the infections difficult to treat with conventional antibiotics.