抄録
It has been reported that statins increase osteogenic effects by inhibiting the cholesterol synthesis pathway. However, statins are unsuitable for local administration by themselves due to their rapid release in vivo. In order to develop the optimal concentration of fluvastatin-gelatin complexes for use as new osteogenic drugs, the purpose of this study was to investigate the coupled state of fluvastatin with gelatin in vitro. The coupling capacity of fluvastatin with gelatin was determined by measuring the remnant fraction of fluvastatin by ultrafiltration. Fluvastatin was dissolved at various concentrations (100, 200, 300, 400 and 500 µM) into a 3-mg/ml gelatin solution. The complexes (500 µl) of fluvastatin solution and gelatin solution were filtered using a centrifugal ultrafilter at 15000 g in a swing-bucket rotor. The complexes were divided into an ultrafiltrated fraction containing fluvastatins freely released from the complex and a remnant fraction containing fluvastatin coupled with gelatin. The absorbance of the fluvastatin in the ultrafiltrated fraction was measured at 303 nm with an ultraviolet–visible transmission spectrophotometer. The fluvastatin-coupling capacity was then calculated based on a standard curve representing absorbance value vs. fluvastatin concentration. In addition, the osteogenic activity of fluvastatin coupled with gelatin was measured through the HMG-CoA reductase inhibitory activity in the cholesterol synthesis pathway. The results showed that a molecule of gelatin has coupling ability for a specific amount of fluvastatin (291 µM fluvastatin/ 3 mg gelatin). The fluvastatin-gelatin complex had the same osteogenic activity as separately used fluvastatin through the inhibition of HMG-CoA reductase.
