Development of Biodegradable Hydrogels for the Controlled Release of Antimicrobial and Antioxidant Agents

Antibiotic resistance emergence is a major medical challenge due to the resulting reduced clinical effectiveness of antibiotics.  Mitigation of these resistant bacteria in wounds would be greatly beneficial towards the reduction of infection and prognosis of patients.  In this research, a multidrug loaded hydrogel is devised which can interfere with the ability of Staphylococcus aureus to develop antibiotic resistance towards the commonly used antibiotic vancomycin.  By acting upon the bacteria with two agents which function through independent mechanisms, it is possible to suppress the ability of bacteria to propagate as well as evolve resistance via hydrogen peroxide signaling in formed biofilms.  Sustained release of the drugs is important as eventually the hydrogel will have a longer life-span in vivo versus a burst-release system, and these two components are shown to time-release by adding them to a tunable biodegradable poly(beta-amino ester) hydrogel.  This time-release is shown through use of degradation studies in PBS as well as through zone of inhibition via hydrogel diffusion onto S. aureus seeded blood agar petri dishes.  Preliminary data is presented upon the experimental design of showing the reduction of antibiotic resistance emergence with multidrug loaded hydrogels.  The synergistic effect of vancomycin and catalase released from a hydrogel illustrates that this system is potentially effective in vivo as an infection reducing and preventing medical device.