Biological Activities of Sustained Polymyxin B Release from Calcium Phosphate Biomaterial Prepared by Dynamic Compaction: an in Vitro Study

Calcium phosphate ceramics (CaP) have recently been proposed as a potential matrix for a bioactive drug delivery system (DDS) in which the effect in situ of a released therapeutic agent is favored by the biocompatibility, osteoconductivity, and bioresorption of the ceramic material. Polymyxin B (PMB) is a polypeptidic antibiotic which undergoes thermodamage above 60 degrees C. The dynamic compaction method was developed to consolidate the drug load on CaP powder without external heating. Two projectile velocities (50 and 25 m/s) were used here to achieve powder consolidation. Among the different techniques used to associate therapeutic agents with CaP, wet adsorption was performed before the dynamic compaction process. The PMB release profile was measured by a capillary electrophoresis technique, CaP crystallography was studied by x-ray diffraction, and CaP physicochemical analysis was performed by infrared spectroscopy. The biological activities of PMB-loaded compacted CaP were determined by the effect of the antibiotic and monocyte/macrophage degradation on compact surfaces. PMB release began after 2-3 days of incubation for blocks compacted at 25 m/s velocity and on day 5 for those compacted at 50 m/s velocity. A discrepancy was noted between the amounts of PMB released (0.5-2.1 mg) and the amounts initially compacted (2-8 mg) with CaP powder. The biological activities (antibacterial activity and inhibited lipopolysaccharide effects on monocyte/macrophage CaP degradation) of PMB released from compacted calcium-deficient apatite were unaltered. Thus, dynamic compaction allows PMB to be used with CaP ceramics without any loss in its integrity and biological effects.