title: Sustained release of simvastatin from premixed injectable calcium phosphate cement.
abstract: 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.
authors.affiliation: Division of Applied Materials Science, Department of Engineering Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Maryam
authors.initials: M
authors.lastname: Montazerolghaem
authors.forename: Håkan
authors.initials: H
authors.lastname: Engqvist
authors.forename: Marjam
authors.initials: M
authors.lastname: Karlsson Ott
mesh_terms: D001843:Bone Cements / Q000737:chemistry / Q000494:pharmacology*; D002130:Calcium Phosphates / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D019245:Compressive Strength; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D010012:Osteogenesis / Q000187:drug effects*; D019821:Simvastatin / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D001843:Bone Cements; D002130:Calcium Phosphates; D003692:Delayed-Action Preparations; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C020243:calcium phosphate; D019821:Simvastatin
keywords: Saos-2 cells; calcium phosphate cement; drug release; osteogenesis; simvastatin