Encapsulation of simvastatin in PLGA microspheres loaded into hydrogel loaded BCP porous spongy scaffold as a controlled drug delivery system for bone tissue regeneration

J Biomater Appl. 2014 Apr;28(8):1151-63. doi: 10.1177/0885328213499272. Epub 2013 Sep 12.

Abstract

The main objective of this study was to fabricate a controlled drug delivery which is simultaneously effective for bone regeneration. We have encapsulated simvastatin, which enhances osteoblastic activity, in the poly (lactic-co-glycolic acid) microspheres. Loading of these microspheres inside the spongy scaffold of biphasic calcium phosphate with the help of Gelatin (Gel) hydrogel controls the delivery of the drug, and ensures a more favorable drug release profile. As a result, some significant benefits have been achieved, such as higher mechanical strength, excellent biocompatibility in in vitro experiments. For determining the characteristics of the composite scaffold, several analysis, such as scanning electron microscope, EDX, X-ray diffraction, FT-IR, and porosity were carried out. The in vitro drug release profile clearly indicates that simvastatin release from the microsphere was more controlled and prolonged after loading in the scaffold. Biocompatibility was certainly higher for the final composite scaffold compared to drug unloaded scaffold, as assessed through MTT assay and Confocal imaging with MC3T3-E1 pre-osteoblast cells. Cell attachment and proliferation were certainly higher in the presence of drug loaded microspheres. Bone remodeling gene and protein expression were observed by real-time polymerase chain reaction and Western blot respectively. Simvastatin loaded scaffold exhibited the best results in every determination which was carried out.

Keywords: BCP; PLGA; Sponge replica; drug delivery; scaffold; simvastatin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Bone Regeneration / drug effects*
  • Bone Regeneration / genetics
  • Bone Regeneration / physiology
  • Drug Carriers / chemistry
  • Drug Compounding
  • Drug Delivery Systems*
  • Gene Expression / drug effects
  • Hydrogels
  • Hydroxyapatites
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage*
  • Lactic Acid*
  • Materials Testing
  • Mice
  • Microscopy, Electron, Scanning
  • Microspheres
  • Osteoblasts / cytology
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism
  • Polyglycolic Acid*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Simvastatin / administration & dosage*
  • Tissue Scaffolds / chemistry

Substances

  • Drug Carriers
  • Hydrogels
  • Hydroxyapatites
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • hydroxyapatite-beta tricalcium phosphate
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Simvastatin