The use of bone cement for the localized, controlled release of the antibiotics vancomycin, linezolid, or fusidic acid: effect of additives on drug release rates and mechanical strength

Bone cement containing antibiotics is commonly used to treat orthopedic related infections. However, effective treatment (especially of resistant bacteria, methacillin-resistant Staphylococcus aureus (MRSA)) is compromised by very low levels of drug release so that typically less than 10% of loaded drug is released over a 6-week period. The objective of this study was to investigate the effect of incorporation of water soluble excipients (polyethylene glycol, sodium chloride, or dextran) into antibiotic-loaded cement on mechanical strength and drug release properties. Poly(methyl methylacrylate) cement implants containing various amounts of drug (vancomycin, linezolid or fusidic acid (all MRSA active)) and excipients were cast in the form of beads or films and characterized using differential scanning calorimetry. Mechanical strength as assessed by Young's modulus was determined by thermo-mechanical analysis. Drug release was measured by incubation in phosphate buffered saline with analysis by HPLC methods. The inclusion of sodium chloride up to 20% w/w caused only minor reductions in Young's modulus. Vancomycin and linezolid released very slowly from unmodified bone cement beads (less than 3% released by 4 weeks) whereas fusidic acid released more quickly (approximately 8% released by 4 weeks). The inclusion of sodium chloride or dextran in bone cement resulted in major increases in the release rate of vancomycin, linezolid and fusidic acid. These studies support the inclusion of sodium chloride and dextran in bone cement to increase the release rate of vancomycin, linezolid, or fusidic acid without compromising the mechanical strength of the composite material.