Infection responsive coatings to reduce biofilm formation and encrustation of urinary catheters

Aims: The care of patients undergoing long-term urethral catheterization is frequently complicated by Proteus mirabilis infection. This organism forms dense, crystalline biofilms, which block catheters leading to serious clinical conditions. However, there are currently no truly effective approaches to control this problem. Here, we describe the development of a novel theranostic catheter coating, to simultaneously provide early warning of blockage, and actively delay crystalline biofilm formation. Methods and Results: The coating comprises of a pH sensitive upper polymer layer (poly(methyl methacrylate-co-methacrylic acid); Eudragit S 100(r)) and a hydrogel base layer of poly(vinyl alcohol), which is loaded with therapeutic agents (acetohydroxamic acid or ciprofloxacin hydrochloride) and a fluorescent dye, 5(6)-carboxyfluorescein (CF). The elevation of urinary pH due to P. mirabilis urease activity results in the dissolution of the upper layer and release of cargo agents contained in the base layer. Experiments using in vitro models, which were representative of P. mirabilis catheter-associated urinary tract infections, demonstrated that these coatings significantly delay time taken for catheters to block. Coatings containing both CF dye and ciprofloxacin HCl were able to provide an average of ca. 79 h advanced warning of blockage and extend catheter lifespan ca. 3.40-fold. Conclusions: This study has demonstrated the potential for theranostic, infection-responsive coatings to form a promising approach to combat catheter encrustation and actively delay blockage. Significance and Impact of Study This study builds on previous research conducted in our group and further optimizes the proposed, infection responsive, urinary catheter coating. For the first time, therapeutic agents have been incorporated into this theranostic coating design. This resulted in an advancedwarning of blockage (e.g., dye release) and actively delays catheter blockage times (e.g., therapeutic agent release into the bladder). Such coatings represent a major advance in the treatment of catheter-associated urinary tract infections (CAUTIs).