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.

A slow and sustained release of methotrexate (MTX) from a new polymeric dicalcium phosphate dehydrate cement (P-DCPD)

“…plays a critical role in the mechanical performance of P-DCPD. For example, loading of erythromycin 28 and/or tobramycin 27 at high concentration (10% wt/wt) had little impacts on the mechanical performance of P-DCPD. Doxorubicin is one of the effective and broad spectrum anticancer drugs.…”

“…25 To the best of our knowledge, no ceramic cement using similar technologies has been reported before. P-DCPD represents a new bone void filler with significant advantages, including strong mechanically strength, 26 excellent cohesion, 24 as well as a mean of sustained drug delivery 27,28 because of its unique ionic binding and intrinsic entanglement of polyphosphate chains with embedded drugs. 29 The handling properties of P-DCPD is similar to PMMA cement and other commercially available CPCs.…”

Repair of a rat calvaria defect with injectable strontium (Sr)‐doped polyphosphate dicalcium phosphate dehydrate (P‐DCPD) ceramic bone grafts

“…12 The compressive strength of the material tested without any drug ranged between 60 and 70 MPA. 12 P-DCPD represents a promising means of tailoring drug delivery, in particular, antibiotics, 15,16 due to its ionic binding and intrinsic disentangled polyphosphate chains. 15 Strontium (Sr), a minor element, is found naturally in human bodies and in our diets.…”