OCR Text |
Show COLLEGE OF PHARMACY UNDERGRADUATE RESEARCH ABSTRACTS Jason DeGooyer David W. Grainger Amanda Brooks 58 POLYMER-CONTROLLED EXTENDED COMBINATION RELEASE OF SILVER AND CHLORHEXIDINE FROM A BONE VOID FILLER Jason DeGooyer (David W. Grainger, Amanda Brooks) Department of Bioengineering Department of Pharmaceutics and Pharmaceutical Chemistry University of Utah Despite the best efforts of clinicians working with material and pharmaceutical scientists, there remains a 1 - 3 % risk of developing osteomyelitis, a deep bone infection, during bone graft procedures. Although this rate seems low, the overall increase in the number of orthopedic procedures requiring bone graft is increasing and so the absolute number of osteomyelitis complications is also increasing. In order to combat the challenge of bone graft-associated osteomyelitis, Dr. David Grainger's lab has been developing a novel implantable, polymer-controlled local drug releasing bone graft filler system. This matrix is a combination of clinically familiar ceramic-based bone void filler plus the biocompatible polymers, poly-caprolactone (PCL) and polyethylene glycol (PEG), and a variety of clinically familiar antibiotics. Several traditional antibiotics have proven successful in microbiological zone of inhibition in vitro studies (ZOI) against Staphylococcus aureus (ATCC strain 49230). Because historically silver and chlorhexidine have been used in combination against Staphylococcus infections in implanted biomedical catheters, the clinical success of these drugs in reducing catheter-related infections provided the impetus to incorporate them into the bone graft drug-releasing implant described here. In this study, the common antiseptic chlorhexidine and a variety of bacteriostatic silver compounds were incorporated into a ceramic-polymer bone filler composite material to provide synergistic antimicrobial activity upon release. This was intended to better inhibit S. aureus infections. Silver chloride was used in combination with the antiseptic chlorhexidine to test for synergistic or enhanced antimicrobial bioactivity against S. aureus beyond that seen with either individual compound. Antimicrobial results out to 12-weeks for the in vitro drug release and killing study showed that 6 7 % of the ZOIs were indeed synergistic, confirming the original hypothesis that this degradable bone matrix filler is a suitable system for the release of multi-drug cocktails to locally prevent implant infections in bone. This experiment has served to further broaden the list of drugs released from this biomaterial bone graft implant technology. A myriad of other drug interactions should n o w be tested in this novel system in order to broaden the number of pathogens it is capable of fighting in the context of osteomyelitis. |