Antimicrobial Polymers for Catheter Coatings

Abstract

People suffering from urinary tract disorders often rely on urinary catheters for proper voiding of their bladder. However, the use of such medical devices are connected with an increased risk of contracting urinary tract infections (UTI). Administration of antibiotics are used in the treatment of such patients but the repeated use of these medications have shown to be leading to antibiotic resistant bacteria. The painful and reoccurring infections is a severe limitation in their everyday life and measures to prevent this have revolved around antimicrobial coatings that releases antibiotics or repel adhesion of bacteria but have shown limited effect. Cationic polymer surfaces have emerged as an alternative solution able to kill bacteria in direct contact and thereby avoids depletion by release of an active compound. Especially quaternary ammonium polymer coatings have been exploited for their antimicrobial activity and investigation and application of such systems in relation to urinary catheter coatings to reduce or prevent catheter associated urinary tract infections (CAUTI), is the focus of this dissertation. Initially, a screening platform able to conduct surface modification directly onto polyurethane (PU) catheter material, was developed to investigate grafting conditions of monomers via an industrially relevant process. Here, the combination and concentration of monomers proved to be important parameters for the outcome of the polymerization. The design of the device also allowed for detailed chemical analysis and characterization of the surface by both water contact angle analysis (WCA), x-ray photoelectron spectroscopy (XPS), Fourier-transform infrared spectroscopy (FT-IR) and UV-vis spectroscopy. The platform thereby proved to be a suitable tool for exploring large variations in grafted polymer coatings. In the next step, the platform was utilized for the preparation of a series of quaternary ammonium based coatings on PU and was used to establish a suitable bacteriological methodology for the evaluation of the antimicrobial activity. A long range of different assays were applied but the chemical nature of PU as well as diffusion of process aids lead to inconclusive results. A method for conducting high throughput screening of quaternary ammonium modified PU was therefore, in this case, not possible using conventional methods. Alternatively, polydimethylsiloxane (PDMS) was chosen as a more inert catheter substrate and used for the development of a controlled surface initiated supplemental activation reducing agent atom transfer radical polymerization (SI-SARA-ATRP) technique. This method was applied to gain a more fundamental understanding of the structure-property relationship relating to the antimicrobial activity of quaternized 2-(dimethylamino)ethyl methacrylate (DMAEMA) polymer systems. The effect of brush length and choice of alkylation agent showed that charge density, mobility and amphiphilicity were pivotal for achieving highest possible antimicrobial effect. As a final part of the thesis, quaternary ammonium polymers were implemented as an additive in existing Coloplast coating formulations to evaluate their applicability in production of antimicrobial urinary catheters. Initial investigations were made on flat polymer substrates, which showed that antimicrobial activity increased with increasing content of the quaternary ammonium polymer and retained activity even after exposure to E-beam sterilization treatment. Applying the coating directly onto urinary catheters gave both smooth low friction surfaces and an evenly distributed polymer layer. This proved that quaternary ammonium polymers could be incorporated in an industrial process for production of smooth hydrophilic catheter coatings. However, in disagreement with previous results, reduced antimicrobial activity was seen for quaternary ammonium containing coatings. The lack of antimicrobial activity for quaternary ammonium polymers in combination with hydrophilic coatings, was attributed to high water uptake and swelling of the system. This could dilute the charge density resulting in diminished effect. This is, however, a subject for further investigation to clarify the precise cause for the observed trend.