Sustained curcumin release from PLGA microspheres improves bone formation under diabetic conditions by inhibiting the reactive oxygen species production

Drug Des Devel Ther. 2018 May 24:12:1453-1466. doi: 10.2147/DDDT.S154334. eCollection 2018.

Abstract

Background: Excessive reactive oxygen species production caused by type 2 diabetes conditions can disrupt normal bone metabolism and greatly impair bone regeneration.

Materials and methods: In the present study, curcumin (Cur)-loaded microspheres were incorporated into a fish collagen nano-hydroxyapatite scaffold to promote bone repair under diabetic conditions by inhibiting the reactive oxygen species production.

Results: The drug release kinetic study showed that the Cur release from the composite scaffolds lasted up to 30 days. The sustained curcumin release from the scaffold significantly inhibited the overproduction of reactive oxygen species in mesenchymal stem cells caused by diabetic serum. Moreover, the Cur-loaded scaffold also remarkedly alleviated the negative effects of diabetic serum on the proliferation, migration, and osteogenic differentiation of mesenchymal stem cells. When implanted into bone defects in type 2 diabetic rats, the Cur-loaded scaffold also showed a greater bone formation capability compared to the pure scaffold.

Conclusion: The results of this study suggested that the novel controlled Cur release system may provide a promising route to improve bone regeneration in type 2 diabetic patients.

Keywords: PLGA; bone repair; curcumin; drug delivery system; type 2 diabetes mellitus.

MeSH terms

  • Animals
  • Bone Marrow / drug effects
  • Bone Marrow / metabolism
  • Bone Marrow / pathology
  • Bone Regeneration / drug effects*
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Curcumin / administration & dosage
  • Curcumin / chemistry
  • Curcumin / pharmacology*
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology
  • Dose-Response Relationship, Drug
  • Male
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Mesenchymal Stem Cells / pathology
  • Microspheres
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemistry*
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / antagonists & inhibitors*
  • Reactive Oxygen Species / metabolism
  • Structure-Activity Relationship

Substances

  • Reactive Oxygen Species
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Curcumin