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

Abstract

A novel and injectable polymeric dicalcium phosphate dehydrate cement (P-DCPD) was developed that is mechanically strong and has excellent cohesion. Methotrexate (MTX) is an anticancer drug for many tumors including bone cancer. The current study assessed the performance of MTX loaded P-DCPD (MTX-P) in vitro. The applied properties of MTX-P include MTX release, effects on cell viability of human breast cancer MCF 7 cells and murine osteoblastic MC3T3 cells. The impacts of MTX-P on the injectability, setting time, material microstructure and mechanical strength were also evaluated. A slow and sustained MTX release from MTX-P was observed. Eluents collected from MTX-P were cytotoxic to MCF7 cells. MT3T3 cells, however, were much less sensitive to MTX-containing eluents. MTX-P was injectable. A remarkable delay of the setting time was observed in 0.5% MTX-P (45.7 ± 1.9 min) and 1% MTX-P (49.5 ± 3.4 min) as compared to control-P (11.8 ± 1.2 min), respectively. The compressive strength was significantly reduced in 0.5% MTX-P (16.49 ± 2.43 MPa) and in 1% MTX-P (10.68 ± 3.97 MPa) as compared to control-P (53.09 ± 8.64 MPa). The inferior performance of MTX-P observed might be due to the insufficient crystal formation and uneven distribution of MTX within P-DCPD matrices. Our data may shed some light on the future application of MTX-P in the treatment of bone defects after tumor excision with a plethora of applications by including other anticancer drugs because of its safety and degradability. Further material optimization and in vivo validation are required to achieve a clinically applicable product.