Levofloxacin impregnation and extended release: Concentration model for insulin catheters

Abstract

Increasing the lifetime of percutaneous insulin delivery catheters to minimize painful needle sticks increases the risk of infection. To combat surface-adherent bacteria and potential biofilm formation, we developed a method to impregnate levofloxacin antibiotic into the outer polymer of the catheter so that it can leach into the external medium. Complementarily, we developed a method to quantify the concentration of antibiotic to ensure the minimum inhibitory concentration (MIC) is maintained throughout the duration of catheter use. Additionally, we have investigated the extent of antibiotic resistance after a zwitterionic nonfouling coating treatment to ensure suitable release after further surface modification. Levofloxacin was incorporated into the catheter through the swelling of the outer polyurethane of the bilayer catheter and subsequent solvent evaporation. The zone of inhibition was measured over time with S. epidermidis on LB agar plates. The release of levofloxacin was measured using optical absorbance spectroscopy in water and quantified against a linear standard curve at 292 nm. We developed a model using Fick's second law of diffusion to calculate the concentration around the catheter. Visible inhibition of bacterial growth and biofilm formation was shown for up to 38 days. A total of 8–45 µg of antibiotic was released over 26 days and a concentration of 820,000 µg/mL in the 0.17 µL control volume was reached at day 26 for the minimally-loaded samples, an amount many orders of magnitude greater than the MIC. After the nonfouling treatment, the lowest concentration reached was 16 µg/mL after 26 days. In conclusion, we have demonstrated a suitable method to induce antibacterial activity for insulin catheters, maintain the MIC, and sustain antibacterial character following further surface coatings.