Development and effect of a sustainable and controllable simvastatin-releasing device based on PLGA microspheres/carbonate apatite cement composite: In vitro evaluation for use as a drug delivery system from bone-like biomaterial

Abstract Carbonated apatite cement can be a potential biomaterial to be used as a drug carrier. We reported previously that sustainable release of simvastatin (SIM) from poly(lactic-co-glycolic acid) (PLGA) formulations could induce bone formation. The aim of this study was to develop a SIM-loaded PLGA microspheres (SPLGAMs)/carbonated hydroxyapatite (CHAP) composite, and investigate the effect of SIM released from that composite in comparison with a SIM/CHAP composite used as a control. X-ray diffraction analysis (XRD) and Fourier-transformed infrared spectroscopy (FT-IR) results showed most parts of the cement bulk powder transformed into carbonated hydroxyapatite. The SPLGAMs and SPLGAMs/CHAP composites were able to produce sustained release of SIM for 1 month, whereas the SIM/CHAP composite released SIM for 2 weeks. The mechanisms of the drug release patterns from these composites were confirmed by several mathematical models. The proliferation of MC3T3-E1 cells on the SPLGAMs/CHAP composite showed no significant difference in comparison with the SIM/CHAP composite. However, the SPLGAMs/CHAP composite significantly increased alkaline phosphate activity, a differentiation marker of MC3T3-E1 cells, compared with the SIM/CHAP composite. These results suggested that the SPLGAMs/CHAP composite could release SIM sustainably and induce proliferation and differentiation of MC3T3-E1 more effectively than the SIM/CHAP composite.