Polyurethanes adsorbed with cefamandole nafate and fluconazole to inhibit the formation of polymicrobial biofilms.

Searching for a strategy to inhibit the formation of polymicrobial (bacterial and fungal) biofilms on medical devices, we planned experiments based on the combined adsorption of an antibiotic and an antifungal drug to functionalized polyurethanes. Cefamandole nafate (CEF) and fluconazole (FLU) were chosen as model molecules due to their solubility in water and polar nature which enable them to interact with polymers by hydrogen bonds. Four newly synthesized polyurethanes having different functional groups in the side-chain (carboxyl, hydroxyl, primary amino and sulphate groups) were employed as round shaped disks to adsorb cefamandole and fluconazole either alone or in combination. The correlation between the strength of polymer-drug interactions and the amount of drug release was assessed by kinetics studies. The antimicrobial activity of polymers loaded with FLU and CEF was tested against two reference strains of Candida albicans (ATCC 90028) and Staphylococcus epidermidis (ATCC 35984) by the Kirby Bauer test and scanning electron microscopy (SEM). Among the tested ones, polymers possessing amino- and sulphate- groups were able to absorb higher amounts of both CEF and FLU by establishing hydrogen bond and van der Waals interactions. The antimicrobial activity of CEF-loaded polymers lasted from 5 days for the amino group- containing polymer to 7 days for the sulphate group-containing polymer. As for the FLU-loaded polymers, their antifungal activity lasted for 1-2 days, indicating a poor drug release. Instead, the sulphate group-containing polymer absorbed with the two drugs were able to exhibit a 4 days antifungal activity. In this last case, the inhibition zone, as measured by the Kirby Bauer test, resulted to be 32 mm after 1 day, rapidly decreasing to 20 mm on the second, to 3 mm on the third and to 1 mm on the fourth day. These data were confirmed by SEM observations. The establishing of polar interactions between the drugs and the polymer allowed the adsorption of higher drug amounts while the polymer hydrophylicity promoted the release of higher drug concentrations. The greater antifungal effect of fluconazole which can be obtained by the simultaneous treatment with CEF, as observed in our experiments, needs further investigation. Therefore, our future experiments will explore the mechanism of this synergistic effect into more depth. In fact, this finding might open innovative perspectives for prevention and treatment of medical device-related infections supported by fungal species.