Controlled release of simvastatin-loaded thermo-sensitive PLGA-PEG-PLGA hydrogel for bone tissue regeneration: in vitro and in vivo characteristics

J Biomed Mater Res A. 2015 Nov;103(11):3580-9. doi: 10.1002/jbm.a.35499. Epub 2015 May 29.

Abstract

Reports on the local delivery of drug loaded injectable hydrogels for bone regeneration are currently limited. This study assessed the effect of controlled simvastatin (SIM) release from a thermo-sensitive hydrogel in vitro and in vivo. We successfully manufactured and evaluated thermo-sensitive poly(d,l-lactide-co-glycolide)-poly(ethylene glycol)-poly(d,l-lactide-co-glycolide) triblock copolymers (PLGA-PEG-PLGA) loaded with SIM. The osteogenic effect of this hydrogel was tested in vitro and in vivo. MC-3T3 E1 cells proliferation and osteoblastic differentiation was analyzed after cultivation with the hydrogel extracts. Cells co-cultured with SIM/PLGA-PEG-PLGA extracts showed an increase in mineralization and osteogenic gene expression compared to the other two groups. Additionally, the characteristics of this composite in vivo were demonstrated using a rat bone defect model. The bone defects injected with SIM/PLGA-PEG-PLGA hydrogel showed increased new bone formation compared to samples treated with PLGA-PEG-PLGA and control samples. The results of this study suggest that SIM/PLGA-PEG-PLGA might provide potential therapeutic value for bone healing.

Keywords: PLGA-PEG-PLGA; bone; drug delivery; simvastatin; thermo-sensitive.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Animals
  • Anthraquinones / metabolism
  • Bone Regeneration / drug effects*
  • Cell Differentiation / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Delayed-Action Preparations
  • Drug Liberation
  • Gene Expression Regulation / drug effects
  • Hydrogel, Polyethylene Glycol Dimethacrylate / chemistry*
  • Male
  • Mice
  • Osteoblasts / cytology
  • Osteoblasts / drug effects
  • Osteoblasts / enzymology
  • Osteogenesis / drug effects
  • Osteogenesis / genetics
  • Polyethylene Glycols / chemistry*
  • Polyglactin 910 / chemistry*
  • Proton Magnetic Resonance Spectroscopy
  • Rats, Wistar
  • Real-Time Polymerase Chain Reaction
  • Simvastatin / administration & dosage*
  • Simvastatin / pharmacology*
  • Spectroscopy, Fourier Transform Infrared
  • Temperature*
  • X-Ray Microtomography

Substances

  • Anthraquinones
  • Delayed-Action Preparations
  • poly(lactic-co-glycolic acid)-polyethylene glycol-poly(lactic-co-glycolic acid)
  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • Polyglactin 910
  • Polyethylene Glycols
  • alizarin
  • Simvastatin
  • Alkaline Phosphatase