Simvastatin Release from Poly(lactide-co-glycolide)

Statins, a group of potent inhibitors of 3-hydroxy-3-methylglutaryl Coenzyme A reductase in cholesterol biosynthesis pathway, have been widely used as a cholesterol lowering drug. The plieotrophic effect of statins on bone metabolism in long-term usage has been begun to be studied during recent years and several in vitro and in vivo studies have demonstrated the ability of statins to promote expression of bone morphogenetic protein-2 (BMP-2), inhibition of osteoclast differentiation and reduction of osteoporotic fractures risk. The high liver specificity and low oral bioavailability of statins, leading to poor peripheral distribution, are the main obstacles to benefit anabolic effects of hydrophobic statins on bone formation. Therefore, developing new administration roots for direct delivery to achieve optimum concentration in the bone microenvironment is of interest. Here we present and compare two approaches of combining statins with bone tissue engineering scaffolds. Simvastatin was combined with a poly(lactide-co-glycolide) (PLGA) membrane scaffold for diffusion-controlled release by dissolving simvastatin (dis-sim) in the membrane casting dope, and for degradation-controlled release by covalently bonding saponifiedsimvastatin (sap-sim) to the PLGA in the spinning dope. Rheological and concentration-dependent membrane morphology changes were observed with saponifiedsimvastatin, suggesting ester bond cleavage and covalent bonding of the statin to the PLGA, but not with dissolved simvastatin. Dissolved simvastatin membranes OPEN ACCESS Polymers 2010, 2 710 showed a logarithmic decay release profile while the saponifiedsimvastatin membranes showed constant release. It can be concluded that the covalent bonding of simvastatinto PLGA scaffolds is showing potential for use as a controlled releasescaffold for bone tissue engineering.