Facilitated and Controlled Strontium Ranelate Delivery Using GCS-HA Nanocarriers Embedded into PEGDA Coupled with Decortication Driven Spinal Regeneration

Int J Nanomedicine. 2021 Jun 22:16:4209-4224. doi: 10.2147/IJN.S274461. eCollection 2021.

Abstract

Background and purpose: Strontium ranelate (SrR) is an oral pharmaceutical agent for osteoporosis. In recent years, numerous unwanted side effects of oral SrR have been revealed. Therefore, its clinical administration and applications are limited. Hereby, this study aims to develop, formulate, and characterize an effective SrR carrier system for spinal bone regeneration.

Methods: Herein, glycol chitosan with hyaluronic acid (HA)-based nanoformulation was used to encapsulate SrR nanoparticles (SrRNPs) through electrostatic interaction. Afterward, the poly(ethylene glycol) diacrylate (PEGDA)-based hydrogels were used to encapsulate pre-synthesized SrRNPs (SrRNPs-H). The scanning electron microscope (SEM), TEM, rheometer, Fourier-transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS) were used to characterize prepared formulations. The rabbit osteoblast and a rat spinal decortication models were used to evaluate and assess the developed formulation biocompatibility and therapeutic efficacy.

Results: In vitro and in vivo studies for cytotoxicity and bone regeneration were conducted. The cell viability test showed that SrRNPs exerted no cytotoxic effects in osteoblast in vitro. Furthermore, in vivo analysis for new bone regeneration mechanism was carried out on rat decortication models. Radiographical and histological analysis suggested a higher level of bone regeneration in the SrRNPs-H-implanted groups than in the other experimental groups.

Conclusion: Local administration of the newly developed formulated SrR could be a promising alternative therapy to enhance bone regeneration in bone-defect sites in future clinical applications.

Keywords: drug formulation; glycol chitosan; hyaluronic acid; nanoparticles; strontium ranelate.

MeSH terms

  • Animals
  • Bone Regeneration / drug effects*
  • Cell Communication / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / pharmacology
  • Drug Carriers / chemistry*
  • Hyaluronic Acid / chemistry*
  • Hydrogels / chemistry
  • Male
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Particle Size
  • Polyethylene Glycols / chemistry*
  • Rabbits
  • Rats
  • Rats, Wistar
  • Spine / drug effects
  • Spine / physiology*
  • Thiophenes / administration & dosage*
  • Thiophenes / pharmacology*

Substances

  • Delayed-Action Preparations
  • Drug Carriers
  • Hydrogels
  • Thiophenes
  • poly(ethylene glycol)diacrylate
  • strontium ranelate
  • Polyethylene Glycols
  • Hyaluronic Acid