A novel multilayer antimicrobial urinary catheter material with antimicrobial properties

Abstract

Urinary catheters are commonly used in medical practice to drain and monitor urine of patients. However, urinary catheterisation is associated with the risk of developing catheter-associated urinary tract infections (CAUTIs), which can result in life-threatening sepsis that requires antibiotics for treatment. Using the layer-by-layer (LbL) technique, we assembled a multilayer catheter comprising nine quadruple layers (9QL) of alginate, chlorhexidine (CHX), alginate and poly(β-amino ester) (PBAE) built upon an amino-functionalised silicone. The prepared catheter materials were tested for pre-packaged storage conditions and sterilisation techniques. The daily release of CHX was measured at pH 7.4 and pH 5 and simulated urine at 37 °C, which was used to determine the antimicrobial affect. CHX release was detected for a minimum of 14 days in PBS (pH 7.4), pH 5 release media, and simulated urine for the samples tested against storage conditions and sterilisation techniques. Incubation of the prepared material with bacterial cultures for 24 hours restricted bacterial growth compared to incubation with the standard material. The minimum inhibition concentration of CHX for clinically isolated urinary tract infection (UTI) bacterial strains was in the range of 19.4-77.4 µM, at which the released CHX could indirectly prevent bacterial growth for up to 14 days. Based on the daily CHX release from the samples, the hydrolysis of PBAE at pH 5 was gradual, resulting in a greater number of days of preventing bacterial growth, followed by pH 7.4 and then simulated urine. To the best of our knowledge, this is the first report on the use of PBAE in association with a urinary catheter material for the release of an antimicrobial drug.

Fig. 1. (a) Structure of chlorhexidine. (b) Poly(β-amino ester) synthesis and (c) hydrolysis. Made using ChemDraw.

Fig. 2. SEM images of base layer silicone and 9QL silicone (bar = 500 µm at ×100, 50 µm at ×1000 and 20 µm at ×3000).

Fig. 3. Average CHX released after 14 days for each storage condition and incubation release media. Total represents average total CHX contained in 9QL samples. SB = sealed bag, AE = air exposed [mean ± SD, n = 3].

Fig. 4. Percentage of CHX release based on average total CHX contained in 9QL samples for each storage condition in (a) pH 7.4 media, (b) pH 5 media and (c) simulated urine. SB = sealed bag, AE = air exposed [mean ± SD, n = 3].

Fig. 5. Average CHX released after 14 days for each sterilisation technique. Total represents average total CHX contained in 9QL samples [mean ± SD, n = 3].

Fig. 6. Effect of sterilisation techniques on CHX release [mean ± SD, n = 3].

Fig. 7. Bacterial culture growth following incubation with base material and 9QL silicone for 24 hours.