To develop an optimized simvastatin (SV) delivery device for bone regeneration, SV-loaded poly(ethylene glycol)-poly(ε-caprolactone) (PECL) micelles were constructed. The micelles had an average size of 80 nm. The in vitro release behavior of SV from the micelles showed prolonged release compared to the free SV. The following four groups were tested in a cytologic experiment: a free SV group, a SV-loaded micelle group with SV concentrations ranging from 2.5×10(-6) to 2.5×10(-10) M, a drug-free micelle group and a blank control group. The effect of SV-loaded micelles on osteoblast-like MG-63 cells was determined via analysis of cell proliferation, alkaline phosphatase activity, and cell calcification. In addition, the mRNA and protein expression of the BMP-2 gene were determined with real-time fluorescence quantitative polymerase chain reaction and western blot techniques, respectively. The results show that SV-loaded PECL micelles cause effective suppression of the osteoblast early proliferation inhibition, stimulation of osteoblast differentiation and mineralization, and stimulation of the BMP-2 expression. Therefore, SV-loaded PECL micelles are predicted to have great potential in bone regeneration applications.
Copyright © 2012. Published by Elsevier B.V.