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

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• 作者：Takayuki Terukina^a ; Hanae Saito^b ; Yuya Tomita^b ; Yusuke Hattori^a ; Makoto Otsuka^a ; ^{motsuka@mushashino-u.ac.jp}
• 关键词：Bone regeneration ; Simvastatin ; Poly(lactic-co-glycolic acid) microspheres ; Carbonated hydroxyapatite ; Drug delivery system ; Controlled release
• 刊名：Journal of Drug Delivery Science and Technology
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：37
• 期：Complete
• 页码：74-80
• 全文大小：837 K
• 卷排序：37

文摘

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.