Evaluating antibiotic release profiles as a function of polymer coating formulation - biomed 2011.

To address persistent 1-3% infection rates associated with orthopedic implant surgeries, the next generation of bone graft filler materials will no longer pharmacologically silent being endowed as a local drug delivery vehicle to maintain locally high levels of antibiotic. Bone allograft material, used as a structural support to fill the avascular spaces in bone defects, revision surgeries, and traumatic injury, can be used as a drug depot to provide effective antibiotic delivery over the orthopedically relevant six-to-eight week time period. Passive antibiotic coatings, applied in the surgical theater, are quickly depleted from the site, inadvertently promoting the development of drug-resistance. Alternatively, many promising controlled-delivery strategies provide an initial burst release of antibiotic within 24 to 72 hours; however, this remains inadequate to combat the onslaught of ubiquitous pathogens that can persist only to reemerge once drug concentrations fall below the minimal inhibitory concentration (MIC). To improve the longevity of this strategy, a variety of coating techniques were evaluated in which clinically-accepted, FDA-recognized, degradable polycaprolactone (PCL) polymer acts as a rate-controlling membrane to retard the release of the antibiotic tobramycin from allograft bone. Using a combination of dipping and rapid drying, the drug-releasing polymer coating was applied concurrently maintaining the high surface area of the allograft bone; however, SEM imaging reveled an imperfect coating that negatively affected the release kinetics. Altering the drug-containing polymer formulation to incorporate water provided a smoother, more uniform coat and ultimately improved the drug-release profile and longevity out to 5 weeks using both bacteriostatic and bacteriocidal assays. Additionally, drug bioactivity was assessed and confirmed between 2 and 4 weeks in the absence of the water-containing polymer.