Bioactive/Natural Polymeric Scaffolds Loaded with Ciprofloxacin for Treatment of Osteomyelitis

AAPS PharmSciTech. 2017 May;18(4):1056-1069. doi: 10.1208/s12249-016-0605-0. Epub 2016 Aug 12.

Abstract

Local delivery of antibiotic into injured bone is a demand. In this work, different scaffolds of chitosan (C) with or without bioactive glass (G) were prepared using the freeze-drying technique in 2:1, 1:1, and 1:2 weight ratios. Chitosan scaffolds and selected formulas of chitosan to bioglass were loaded with ciprofloxacin in 5%, 10%, and 20% w/w. Scaffold morphology showed an interconnected porous structure, where the glass particles were homogeneously dispersed in the chitosan matrix. The kinetic study confirmed that the scaffold containing 1:2 weight ratio of chitosan to glass (CG12) showed optimal bioactivity with good compromise between Ca and P uptake capacities and Si release rate. Chitosan/bioactive glass scaffolds showed larger t 50 values indicating less burst drug release followed by a sustained drug release profile compared to that of chitosan scaffolds. The cell growth, migration, adhesion, and invasion were enhanced onto CG12 scaffold surfaces. Samples of CG12 scaffolds with or without 5% drug induced vascular endothelial growth factor (VEGF), while those containing 10% drug diminished VEGF level. Only CG12 induced the cell differentiation (alkaline phosphatase activity). In conclusion, CG12 containing 5% drug can be considered a biocompatible carrier which would help in the localized osteomyelitis treatment.

Keywords: Saos-2 cells; bone tissue engineering; drug delivery; kinetics; scaffolds.

MeSH terms

  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacokinetics
  • Biocompatible Materials / chemistry
  • Biocompatible Materials / pharmacology
  • Bone and Bones / drug effects
  • Cell Proliferation / drug effects
  • Ceramics / chemistry
  • Ceramics / pharmacology
  • Chitosan / chemistry
  • Chitosan / pharmacology
  • Ciprofloxacin* / administration & dosage
  • Ciprofloxacin* / pharmacokinetics
  • Drug Delivery Systems
  • Drug Liberation
  • Humans
  • Osteomyelitis / therapy*
  • Porosity
  • Tissue Engineering / methods
  • Tissue Scaffolds / chemistry*

Substances

  • Anti-Bacterial Agents
  • Biocompatible Materials
  • Bioglass
  • Ciprofloxacin
  • Chitosan