INORGANIC MATERIALS FOR LOCAL DRUG DELIVERY

Orthopedic infections, including periprosthetic joint infections and osteomyelitis, are debilitating complications that greatly increase mortality rates and expenditure of healthcare resources. Treatment protocols include surgical debridement of infected tissue, removal of any foreign implants, and several weeks of systemic antibiotic therapy, yet recurrence rates remain high. Local antibiotic delivery systems augment traditional therapy techniques by increasing antibiotic concentrations at the site of infection to levels that are unachievable by IV or oral delivery, thereby improving bacterial clearance rates. Current clinical products are commonly prepared at the surgeons direction, with only limited data and anecdotal reports guiding antibiotic choice and loading. The purpose of this research was to evaluate several local delivery systems, including multiple calcium based bone void fillers already in use and a novel magnetically responsive microbead, to evaluate properties such as drug elution kinetics, biocompatibility, degradation, and adverse effects of drug loading on material handling characteristics. Highlights of the study results include the finding that antibiotic incorporation can affect the hardening of calcium based bone void fillers, with some commonly used antibiotics greatly increasing set time required before use compared to others. This delay in hardening or setting may negatively affect clinical use as the material must be prepared at the time of surgery. Additionally, incorporation of multiple antibiotics can alter the release kinetics compared to when each antibiotic is used alone, potentially affecting the duration of effective elution. Another local drug delivery approach to maximize efficacy of the antibiotic payload is the use of stimuli responsive materials to alter release kinetics. Incorporation of iron oxide nanoparticles into a novel chitosan-polyethylene glycol microbead system allowed drug elution to be increased on demand through the use of alternating magnetic fields to generate heat within the system. External stimulation techniques such as this can alleviate drawbacks of current local drug delivery materials by further improving release kinetics to maximize efficacy of the drug payload