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

Abstract

Aims The care of patients undergoing long-term urethral catheterisation 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 layer of poly(methyl methacrylate-co-methacrylic acid; Eudragit S100®) and a hydrogel base layer of poly(vinyl alcohol), which is loaded with therapeutic agents (acetohydroxamic acid or ciprofloxacin hydrochloride) and the 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 of P. mirabilis catheter infection demonstrated that 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.