In-situ forming chitosan implant-loaded with raloxifene hydrochloride and bioactive glass nanoparticles for treatment of bone injuries: Formulation and biological evaluation in animal model

Int J Pharm. 2020 Apr 30:580:119213. doi: 10.1016/j.ijpharm.2020.119213. Epub 2020 Mar 9.

Abstract

In-situ forming implants receive great attention for repairing serious bone injuries. The aim of the present study was to prepare novel chitosan in-situ forming implants (CIFI) loaded with bioactive glass nanoparticles and/or raloxifene hydrochloride (RLX). Incorporating raloxifene hydrochloride (RLX) as a selective estrogen receptor modulator was essential to make use of its anti-resorptive properties. The prepared formulae were tested for their in-vitro gelation time, drug release, injectability, rheological properties, erosion rate and morphological properties. Results revealed that the formulation composed of 1% (w/v) chitosan with 2% (w/v) NaHCO3 and 1% (w/v) bioactive glass nanoparticles (CIFI-BG) possessed the most sustained drug release profile which extended over four months with low burst release effect compared to the same formulation lacking bioactive glass nanoparticles (CIFI). Selected formulations were tested for their ability to enhance bone regeneration in induced puncture in rate tibia. Results declared that these formulations were able to enhance bone regeneration after 12 weeks in comparison to the untreated tibial punctures and that containing bioactive glass could be considered as novel approach for treatment of serious bone injuries which require long term treatment and internal mechanical bone support during healing.

Keywords: Bioactive glass; Bone injury; Chitosan; In-situ forming implant; Raloxifene hydrochloride.

MeSH terms

  • Animals
  • Bone Density Conservation Agents / administration & dosage
  • Bone Density Conservation Agents / chemical synthesis*
  • Bone Density Conservation Agents / metabolism
  • Bone Regeneration / drug effects
  • Bone Regeneration / physiology
  • Chitosan / administration & dosage
  • Chitosan / chemical synthesis*
  • Chitosan / metabolism
  • Disease Models, Animal
  • Drug Carriers / administration & dosage
  • Drug Carriers / chemistry
  • Drug Carriers / metabolism
  • Drug Compounding / methods*
  • Drug Evaluation, Preclinical / methods
  • Drug Implants / administration & dosage
  • Drug Implants / chemical synthesis
  • Drug Implants / metabolism
  • Glass / chemistry
  • Male
  • Nanoparticles / administration & dosage
  • Nanoparticles / chemistry*
  • Nanoparticles / metabolism
  • Raloxifene Hydrochloride / administration & dosage
  • Raloxifene Hydrochloride / chemical synthesis*
  • Raloxifene Hydrochloride / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Tibia / drug effects*
  • Tibia / injuries
  • Tibia / metabolism
  • Treatment Outcome

Substances

  • 13-93 bioactive glass
  • Bone Density Conservation Agents
  • Drug Carriers
  • Drug Implants
  • Raloxifene Hydrochloride
  • Chitosan