Compaction strategies for modifying the drug delivery capabilities of gelled calcium polyphosphate matrices

Abstract

Calcium polyphosphates (CPPs) have shown potential as drug delivery matrices, particularly in treating bone-related chronic diseases such as osteomyelitis, where maintenance of sufficient bactericidal concentrations at the infected bone site is essential. The objective of this study was to incorporate an additional compaction step as part of a gelling protocol to optimize CPP matrix properties while enhancing their drug delivery capabilities. Vancomycin-loaded CPP powders were produced using a previously established gelling and drying protocol, G1, and then subsequently compacted at prescribed levels (30, 113 or 452 MPa) before subjecting to an additional gelling and drying protocol (G2). The resulting G2 disks were found to be more homogeneous and dense ( p = 0.0013) when compared with corresponding G1 disks, though increases in matrix density did not translate into subsequent increases in tensile strength. The compaction regelling protocol did, however, eliminate the burst release phenomena observed with the G1 disks and further extended the release of vancomycin into a clinically acceptable therapeutic range of 3 weeks. These changes were associated with the increase in visual homogeneity, the increase in density and a more homogenous dispersion of vancomycin within the G2 disks. The ability to modulate this release profile to a limited extent by altering compaction stress, particle size distribution and regelling time was also demonstrated. Overall, the compaction regelling protocol described here, when used in conjunction with an initial gelling step to achieve matrix drug loading, enhances the flexibility and long-term drug delivery capability of this CPP matrix.