Sustained release of simvastatin from premixed injectable calcium phosphate cement

• 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 ofpremixed acidic calcium phosphate cement (CPC) as a delivery system for water-solubilizedsimvastatin. Freeze-dried simvastatin -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 thecement 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 degrees C, a diffusion-controlledrelease 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.

Subject headings

TEKNIK OCH TEKNOLOGIER  -- Medicinteknik -- Medicinsk material- och protesteknik (hsv//swe)

ENGINEERING AND TECHNOLOGY  -- Medical Engineering -- Medical Materials (hsv//eng)

Keyword

simvastatin

calcium phosphate cement

osteogenesis

drug release

Saos-2 cells

Teknisk fysik med inriktning mot materialvetenskap

Engineering Science with specialization in Materials Science

Publication and Content Type

ref (subject category)

art (subject category)