Development of a polymer-based antimicrobial coating for efficacious urinary catheter protection

Abstract

This study reports the development of a polymer-based catheter coating to facilitate controlled release of antimicrobial peptides (AMP) to target both planktonic bacteria and biofilm in the urinary catheter environment. Catheter associated urinary tract infection (CAUTI) is a common nosocomial infection among hospitalized patients and is a major reservoir of antimicrobial resistant pathogens. Although silver- or antibiotics-coated catheters have been deployed to minimise CAUTI, the inconsistency and lack of durability in antibacterial properties of these coatings have limited their clinical use. The incorporation of AMPs in catheter coatings has gained interest due to the effective bacteria killing effects of AMPs, with few reports on bacterial resistance development against peptides. This study aims to deploy a novel and potentially cost-effective technique to coat an anhydrous polymeric coating impregnated with AMPs for silicone-based catheters, to overcome limitations in conventional hydrogel-based coatings. Sustained peptide release was achieved with the development of an Ethyl Cellulose (EC): 1-Palmitoyl-2-oleoylphosphatidylcholine (POPC)-based diffusion layer over an AMP-laden Polycaprolactone (PCL)-based layer to control AMP diffusion into the environment over a clinically relevant duration. The ‘AMP-EC-PCL’ coating showed good anti-bacteria performance against uropathogenic Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa for up to 6 days. The coating also showed excellent anti-biofilm capability against green fluorescent protein (GFP)-tagged UTI E. coli. Fifteen centimeter catheter segments of single layer ‘AMP-EC-PCL’-coated catheters showed sustainable AMP release kinetics up to 7 days, where good antibacterial and anti-biofilm activity against E. coli was observed. The full scale ‘AMP-EC-PCL’-coated catheter showed improved mechanical integrity compared to commercial silicone catheters with preservation of the catheter balloon integrity upon expansion. Wound healing studies of the coated PDMS samples in mice models showed a reduction in bacteria concentration as compared to uncoated PDMS, indicating in vivo efficacy potential of the developed catheter coating platform.