Application of Novel DOPA-containing Antimicrobial Polymers for the Prevention of Uropathogen Attachment to Urinary Biomaterials.

Introduction and Objective Urinary catheters and stents are frequently prone to catheter-associated urinary tract infections (CAUTI) through biofilm formation. Several strategies have been evaluated in search of a stent coating to reliably prevent adherence of bacteria and biofilm. Previous in vivo and in vitro research with methoxylated polyethylene glycol (mPEG) 3,4-dihydroxyphenylalanine (DOPA) copolymer as a candidate coating showed promising results to reduce the bacterial attachment. We aimed to further enhance this antimicrobial activity by adding antimicrobial agents to newly synthetized DOPA-based copolymers Materials and methods Building on our previous experience, novel copolymers were engineered based on DOPA. Quaternary ammonium groups and silver particles were added by crosslinking to increase antimicrobial activity through both kill-by-contact and planktonic killing. After coating polyurethane sheets and measuring contact angles, all candidate coatings were challenged in vitro with an Escherichia coli culture. The most promising coatings were then further evaluated against a panel of 7 clinically relevant uropathogens and planktonic killing and microbial attachment was determined. Results Initially, seven coatings were developed, referred to as Surphys 093-099. The most significant increase in contact angle was identified in Surphys-095 and -098. Surphys coatings S-094, S-095 and S-098 were crosslinked with silver and exhibited profound antimicrobial properties when challenged with E. coli. Further testing demonstrated S-095 to have antimicrobial efficacy against Gram-positive and Gram-negative bacteria at different silver-loading concentrations. The final coating, consisting of a 2mg/ml solution of S-095 crosslinked with 0.25mg/ml AgNO3 appeared to be highly bactericidal showing a ≥99.9% bacterial killing effect, while remaining below cytotoxicity levels Conclusions We were able to engineer DOPA-based copolymers and add quaternary ammonium and silver particles, thus increasing the bactericidal properties of the coating. These coatings have exhibited a biologically significant ability to prevent uropathogens from attaching to biomaterials and represent a realistic opportunity to combat CAUTI.

Journal of endourology. 2019 May 29 [Epub ahead of print]

Roderick A MacPhee, Thomas Tailly, Sai K Vangala, Justin Koepsel, Liam Brennan, Peter A Cadieux, Jeremy Burton, Jeffrey Dalsin, Hassan Razvi, Chris Wattengel

Lawson Health Research Institute, London, Ontario, Canada ; ., Western University, 6221, Urology, London, Ontario, Canada., Western University, 6221, Urology, London, Ontario, Canada ; ., DSM Biomedical, 92848, Exton, Pennsylvania, United States ; ., Lawson Health Research Institute, 151158, London, Ontario, Canada., Western University, 6221, Microbiology and Immunology, London, Ontario, Canada., DSM Biomedical, 92848, Exton, Pennsylvania, United States ; ., Western University, Urology , 268 Grosvenor St. , London, Ontario, Canada , N6A 3N3 ; ., DSM Biomedical, 92848, Exton, Pennsylvania, United States ; .