| Description |
Orthopedic surgeons currently administer powder vancomycin directly over surgical sites in order to mitigate infections. Local antibiotic administration has been effective at reducing infections; however, there have been few preliminary studies investigating the pharmacokinetics of locally delivered powder vancomycin in a bone fracture model. There has been research investigating the potential use of biomaterials, such as hydrogels, as drug delivery vehicles to extend elution times for better prevention of infections and biofilm development. Agarose hydrogels were used specifically in this project due to their high biocompatibility compared to other materials. The aim of this study was to analyze the drug distribution of two different local prophylactic delivery methods involving powder vancomycin and vancomycin loaded agarose hydrogel using an in vivo model. Another aim of this study was to test the drug kinetics of a 3% w/v agarose hydrogel loaded with vancomycin, cefepime, and a combination of the two in vitro. The rats were euthanized at various time intervals and the bone, surrounding muscle, and blood plasma were explanted and analyzed for vancomycin concentration. We observed low systemic concentrations of vancomycin for both delivery methods. The hydrogel delivery method had fluctuating release kinetics compared to the powder delivery method. The minimum inhibitory concentration for vancomycin to be effective was maintained for 24 hours in the muscle and bone for both delivery methods. Dual loading of the antibiotics leads to more stabilized release kinetics of vancomycin compared to single loading of the antibiotic, likely due to cefepime inhibiting the complete elution of vancomycin initially. The study findings will allow physicians to determine optimum time intervals to re-administer antibiotics in order to prevent toxicity and infection simultaneously. The findings will additionally offer kinetic data for antibiotic loaded agarose hydrogels to be used in future prophylactic treatments. |
