A distinctive release profile of vancomycin and tobramycin from a new and injectable polymeric dicalcium phosphate dehydrate cement (P-DCPD)

Abstract

A novel injectable polymeric dicalcium phosphate dehydrate (P-DCPD) cement was developed with superior mechanical strength and excellent cohesion. The purpose of this study was to assess the in vitro performance of P-DCPD loaded with vancomycin (VAN-P), tobramycin (TOB-P) and combination of both (VAN/TOB-P) (10%, w/w). There is a distinctive release profile between VAN and TOB. VAN-P showed decreased initial burst (<30% within 3 d) and sustained VAN release (76% in 28 d). In the presence of TOB (VAN/TOB-P), >90% of VAN was released within 3 d (p < 0.05). Slow and limited TOB release was observed both in TOB-P (<5%) and in TOB/VAN-P (<1%) over 28 d. Zone of inhibition (ZOI) of Staphylococcus aureus growth showed that eluents collected from VAN-P had stronger and longer ZOI (28 d) than that from TOB-P (14 d, p < 0.05). Direct contact of VAN-P, TOB-P and VAN/TOB-P cements displayed persistent and strong ZOI for >3 weeks. Interestingly, the cement residues (28 d after drug release) still maintained strong ZOI ability. P-DCPD with or without antibiotics loading were nontoxic and had no inferior impacts on the growth of osteoblastic MC3T3 cells. VAN-P and TOB-P were injectable. No significant influence on setting time was observed in both VAN-P (11.7 ± 1.9 min) and VAN/TOB-P (10.8 ± 1.5 min) as compared to control (12.2 ± 2.6 min). We propose that a distinctive release profile of VAN and TOB observed is mainly due to different distribution pattern of VAN and TOB within P-DCPD matrix. A limited release of TOB might be due to the incorporation of TOB inside the crystalline lattice of P-DCPD crystals. Our data supported that the bactericidal efficacy of antibiotics-loaded P-DCPD is not only depend on the amount and velocity of antibiotics released, but also probably more on the direct contact of attached bacteria on the degrading cement surface.