Development of an injectable pseudo-bone thermo-gel for application in small bone fractures

Int J Pharm. 2017 Mar 30;520(1-2):39-48. doi: 10.1016/j.ijpharm.2017.01.039. Epub 2017 Jan 31.

Abstract

A pseudo-bone thermo-gel was synthesized and evaluated for its physicochemical, mechanical and rheological properties, with its application to treat small bone fractures. The pseudo-bone thermo-gel was proven to have thermo-responsive properties, behaving as a solution in temperatures below 25°C, and forming a gelling technology when maintained at physiological conditions. Poly propylene fumerate (PPF), Pluronic F127 and PEG-PCL-PEG were strategically blended, obtaining a thermo-responsive delivery system, to mimic the mechanical properties of bone with sufficient matrix hardness and resilience. A Biopharmaceutics Classification System (BCS) class II drug, simvastatin, was loaded in the pseudo-bone thermo-gel, selected for its bone healing properties. In vitro release analysis was undertaken on a series of experimental formulations, with the ideal formulations obtaining its maximum controlled drug release profile up to 14days. Ex vivo studies were undertaken on an induced 4mm diameter butterfly-fractured osteoporotic human clavicle bone samples. X-ray, ultrasound as well as textural analysis, undertaken on the fractured bones before and after treatment displayed significant bone filling, matrix hardening and matrix resilience properties. These characteristics of the pseudo-bone thermo-gel thus proved significant potential for application in small bone fractures.

Keywords: Bone fractures; Controlled drug release; Pseudo-bone thermo-gel; Thermo-responsive.

MeSH terms

  • Clavicle / diagnostic imaging
  • Clavicle / drug effects
  • Drug Delivery Systems*
  • Drug Liberation
  • Fracture Healing / drug effects
  • Fractures, Bone / diagnostic imaging
  • Fractures, Bone / drug therapy*
  • Gels / chemistry
  • Gels / therapeutic use*
  • Humans
  • Poloxamer / chemistry
  • Polyesters
  • Polyethylene Glycols
  • Polypropylenes / chemistry
  • Simvastatin / chemistry
  • Simvastatin / pharmacokinetics
  • Simvastatin / therapeutic use
  • Temperature

Substances

  • Gels
  • Polyesters
  • Polypropylenes
  • poly(ethylene glycol)-poly(caprolactone)-poly(ethylene glycol)
  • Poloxamer
  • Polyethylene Glycols
  • Simvastatin