The effect of simvastatin-loaded methoxy poly(ethylene glycol)-polylactic acid nanoparticles on osteoblasts

Abstract

ObjectiveTo investigate the effect of simvastatin-loaded polymer nanoparticles on osteoblast proliferation and differentiation, and to seek a better pharmaceutical dosage form to improve the osteogenic effect of simvastatin and provide a more practical drug carrier for its clinical application. Methodspolymer nanoparticles were prepared via the modified spontaneous emulsifying solvent diffusion (SESD) method, and the effects of simvastatin-loaded methoxy poly(ethylene glycol)-polylactic acid nanoparticles on osteoblasts were investigated. A 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay was adopted to detect the proliferation abilities of the cells. An enzyme-linked immunosorbent assay was used to detect the amount of alkaline phosphatase (ALP) in the cells. A real-time polymerase chain reaction was used to detect the expression of osteocalcin (OC) and bone morphogenetic protein-2 (BMP-2) messenger ribonucleic acid (mRNA). ResultsThe study found that the proliferation of osteocytes was inhibited in the simvastatin-loaded nanoparticle (Sim-NP) group, and this inhibition was stronger in the Sim-NP than in the simvastatin group; the ALP activity of osteoblasts was increased in both groups, and this increase was stronger in the Sim-NP than in the simvastatin group. The expression of ALP, OC and BMP-2 mRNA was increased in both groups, and this increase was stronger in the Sim-NP than in the simvastatin group. ConclusionThe authors thus posited that the modified Sim-NPs SESD preparation method was simple and reproducible, and the prepared nanoparticles, with uniform distribution, a regular morphology and spherical shape could greatly improve the solubility of simvastatin. The polymer nanoparticle carrier system improved the effect of simvastatin on the proliferation and differentiation of osteoblasts so that the Sim-NPs were systematically applied to target bone tissues. These results provide a new direction for research on the drugs and treatment methods for osteoporosis.