Division of Applied Materials Science, Department of Engineering Sciences, Uppsala University, Uppsala, Sweden.
J Biomed Mater Res A. 2014 Feb;102(2):340-7. doi: 10.1002/jbm.a.34702. Epub 2013 May 14.
Locally applied simvastatin is known to promote bone regeneration; however, the lack of suitable delivery systems has restricted its clinical use. In this study we demonstrate for the first time the use of premixed acidic calcium phosphate cement (CPC) as a delivery system for water-solubilized simvastatin. Freeze-dried simvastatin β-hydroxy acid (SVA) was added to the premixed cement paste in four different doses (1, 0.5, 0.25, and 0 mg SVA/g cement). The addition of the drug did not alter the cement setting time (38 min), compression strength (5.54 MPa), or diametral tensile strength (2.62 MPa). In a release study conducted in phosphate buffered saline at 37°C, a diffusion-controlled release was observed for over a week. Furthermore, the osteogenic effect of the released SVA was demonstrated in vitro. Cell proliferation, alkaline phosphatase activity, and mineralization were assayed after incubation with cement extracts. The lower doses of SVA (0.5 and 0.25 mg SVA/g cement) showed an approximately fourfold increase in mineralization as compared to the control. In conclusion, our findings suggest that premixed acidic CPC is a good option for local delivery of SVA, due to its ability of slowly releasing the drug, leading to a prolonged stimulation of osteogenesis.
局部应用辛伐他汀已被证实可促进骨再生；然而，由于缺乏合适的给药系统，其临床应用受到限制。本研究首次证明了将预混酸性磷酸钙骨水泥（CPC）用作水溶性辛伐他汀的给药系统。将冻干的辛伐他汀β-羟基酸（SVA）以四种不同剂量（1、0.5、0.25 和 0 mg SVA/g 水泥）添加到预混水泥糊中。药物的添加并未改变水泥的凝固时间（38 分钟）、抗压强度（5.54 MPa）或直径拉伸强度（2.62 MPa）。在 37°C 的磷酸盐缓冲盐中进行的释放研究中，观察到超过一周的扩散控制释放。此外，还在体外证实了释放的 SVA 的成骨作用。用水泥提取物孵育后，测定细胞增殖、碱性磷酸酶活性和矿化。与对照组相比，SVA 的较低剂量（0.5 和 0.25 mg SVA/g 水泥）显示出约 4 倍的矿化增加。总之，我们的研究结果表明，预混酸性 CPC 是 SVA 局部给药的一种较好选择，因为它能够缓慢释放药物，从而延长对成骨的刺激。
