Simvastatin‐loaded macroporous calcium phosphate cement: Preparation, <i>in vitro</i> characterization, and evaluation of <i>in vivo</i> performance

Yin, Han; Li, Yonggang; Si, Meng; Li, Jianmin

doi:10.1002/jbm.a.34228

Cited by 16 publications

(25 citation statements)

References 45 publications

(48 reference statements)

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“…In this study, we have shown that incorporation of up to 1 mg SVA/g cement did not alter the setting time, the compression strength, nor the diametral tensile strength of the cement. These results are also in agreement with previous results from Yin et al where they showed that low amounts of simvastatin incorporated in hydroxyapatite cement did not alter the physiochemical properties of the cement. The XRD results showed no difference in the diffractograms; all cements set into monetite which is in accordance with the previous studies done on premixed acidic cements …”

Section: Discussionsupporting

confidence: 93%

Sustained release of simvastatin from premixed injectable calcium phosphate cement

Montazerolghaem

Engqvist

Ott

2013

J Biomedical Materials Res

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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.

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Section: Discussionsupporting

confidence: 93%

Sustained release of simvastatin from premixed injectable calcium phosphate cement

Montazerolghaem

Engqvist

Ott

2013

J Biomedical Materials Res

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“…[44] Another group determined that up to 10% loading of simvastatin into calcium phosphate samples did not significantly affect the compressive strength. [47] The present study had a lower loading of simvastatin (i.e., 2 wt%), however. Thus, direct loading of simvastatin does not affect the overall strength of different materials.…”

Section: Discussionmentioning

confidence: 76%

Tailored sequential drug release from bilayered calcium sulfate composites

Orellana

Puleo

2014

Materials Science and Engineering: C

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The current standard for treating infected bony defects, such as those caused by periodontal disease, requires multiple time-consuming steps and often multiple procedures to fight the infection and recover lost tissue. Releasing an antibiotic followed by an osteogenic agent from a synthetic bone graft substitute could allow for a streamlined treatment, reducing the need for multiple surgeries and thereby shortening recovery time. Tailorable bilayered calcium sulfate (CS) bone graft substitutes were developed with the ability to sequentially release multiple therapeutic agents. Bilayered composite samples having a shell and core geometry were fabricated with varying amounts (1 or 10 wt%) of metronidazole-loaded poly poly(lactic-co-glycolic acid) (PLGA) particles embedded in the shell and simvastatin directly loaded into either the shell, core, or both. Microcomputed tomography (MicroCT) images showed the overall layered geometry as well as homogenous distribution of PLGA within the shells. Dissolution studies demonstrated that the amount of PLGA particles (i.e., 1 vs. 10 wt%) had a small but significant effect on the erosion rate (3% vs. 3.4% per day). Mechanical testing determined that introducing a layered geometry had a significant effect on the compressive strength, with an average reduction of 35%, but properties were comparable to mandibular trabecular bone. Sustained release of simvastatin directly loaded into CS demonstrated that changing the shell to core volume ratio dictates the duration of drug release from each layer. When loaded together in the shell or in separate layers, sequential release of metronidazole and simvastatin was achieved. By introducing a tunable layered geometry capable of releasing multiple drugs, CS-based bone graft substitutes could be tailored in order to help streamline multiple steps needed to regenerate tissue in infected defects.

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“…After 7 days, the proliferation of cells treated with CPC and SCT/CPC was significantly lower than those treated with the SCT‐PLGA‐20 COOH MS/CPC composites. Such results could be ascribed to the fact that macroporosity and interconnective porosity produced by the PLGA MS provided a space for cell to extend and grow . Therefore, SCT‐PLGA MS/CPC composites could be a promising scaffold condition for the growth of osteoblastic cells.…”

Section: Resultsmentioning

confidence: 99%

“…Such results could be ascribed to the fact that macroporosity and interconnective porosity produced by the PLGA MS provided a space for cell to extend and grow. 22 Therefore, SCT-PLGA MS/CPC composites could be a promising scaffold condition for the growth of osteoblastic cells.…”

Section: Resultsmentioning

confidence: 99%

Salmon calcitonin‐loaded PLGA microspheres/calcium phosphate cement composites for osteoblast proliferation

Zhou³

et al. 2017

J of Applied Polymer Sci

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To improve the efficacy of salmon calcitonin (SCT) on disuse osteoporosis‐induced bone fracture, the sustained‐release vehicles delivered to bone fractures should be developed. In this study, SCT‐loaded poly(d,l‐lactic‐co‐glycolic acid) microspheres (SCT‐PLGA MS) with 20 kDa‐COOH and 40 kDa‐COOH (SCT‐PLGA‐20 COOH MS and SCT‐PLGA‐40 COOH MS) are incorporated into calcium phosphate cement (CPC) at various mass ratios. The cumulative release and mechanical properties of SCT‐PLGA MS/CPC composites decrease as PLGA MS/CPC mass ratio increase. Scanning electron microscopy images and the mass loss of composites indicate the MS from 20% SCT‐PLGA MS/CPC composites have mostly degraded after 8 weeks. In addition, SCT released from the 20% SCT‐PLGA‐20 MS/CPC composites significantly facilitate proliferation and differentiation of MC3T3‐E1 cells. In conclusion, 20% SCT‐PLGA‐20 COOH MS/CPC composites exhibit the sustained drug release, proper CPC degradation, good mechanical properties, and preferable osteoblast proliferation, which would be beneficial to their in vivo applications. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45486.

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Simvastatin‐loaded macroporous calcium phosphate cement: Preparation, in vitro characterization, and evaluation of in vivo performance

Cited by 16 publications

References 45 publications

Sustained release of simvastatin from premixed injectable calcium phosphate cement

Sustained release of simvastatin from premixed injectable calcium phosphate cement

Tailored sequential drug release from bilayered calcium sulfate composites

Salmon calcitonin‐loaded PLGA microspheres/calcium phosphate cement composites for osteoblast proliferation

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