Amikacin-loaded vascular prosthesis as an effective drug carrier

Strong covalent immobilization of amikacin on Uni-Graft® DV straight vascular prostheses made of gelatine-sealed poly(ethylene terephthalate) fibres was performed according to procedure described in the Polish Patent No. P-358934. The concentrations of amikacin in sample solutions were estimated either by HPLC or by UV spectroscopy method previously optimized for amikacin measurements. A high correlation was found between these two methods. It was found that the antibiotic was bound in mixed-type way via three types of interactions: strong covalent bonds (dominating amount: 81.84%) and weak interactions: physical adsorption and ionic bonds (18.19%). Even when total amount of physically and ionically attached drug has been released, the remaining covalently bound amount still locally protected the prostheses in vitro against bacteria. The release test was conducted in PBS at pH 7.4 at 37 °C and showed that about 15% of total drug amount was eluted from the matrix during the first 7 days of shaking, then no more antibiotic was released. It suggested that about 85% of amikacin attached to prosthesis modified in mixed-type mode was bound via covalent interactions. A bacterial inhibition test on Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923 and Pseudomonas aeruginosa ATCC 27853 showed inhibition of growth for all strains at low inoculum concentrations up to 30 days as well as high inoculum concentration for E. coli. At high concentrations of S. aureus and P. aeruginosa, the modified prostheses showed slight bacteriostatic effect since 10th day of experiment. Amikacin-modified vascular prostheses might therefore be protected against bacterial infection locally, without long-lasting drug release to human system.