Novel doped calcium phosphate-PMMA bone cement composites as levofloxacin delivery systems

Int J Pharm. 2015 Jul 25;490(1-2):200-8. doi: 10.1016/j.ijpharm.2015.05.038. Epub 2015 May 19.

Abstract

Antibiotic-loaded acrylic bone cements (ALABCs) are well-established and cost-effective materials to control the occurrence of bone and joint infections. However, the inexistence of alternative antibiotics other than those already commercially available and the poor ability to bind to bone tissue hampering its biological function are still major drawbacks of ALABCs clinical application. The concept of this research work is to develop a novel bone cement (BC) drug delivery system composed by Mg- and Sr-doped calcium phosphate (CaP) particles as drug carriers loaded into a lactose-modified acrylic BC, which, to the best of our knowledge, has never been reported. CaP particles are known to promote bone ingrowth and current research is focused on using these carriers as antibiotic delivery systems for the treatment of bone infections, like osteomyelitis. Levofloxacin is a fluoroquinolone with anti-staphylococcal activity and adequate penetration into osteoarticular tissues and increasingly being recommended to manage bone-related infections. Also, the lactose-modified BC matrix, with a more porous structure, has already proved to enhance antibiotic release from the BC inner matrix. This novel BC composite biomaterial has shown improved mechanical integrity, biocompatibility maintenance, and sustained release of levofloxacin, with concentrations over the minimum inhibitory concentration values after a 48h while maintaining antibacterial activity over an 8-week period against Staphyloccocus aureus and Staphyloccocus epidermidis, common pathogens associated with bone infections.

Keywords: Biocompatibility; Biphasic calcium phosphate; Controlled release; Drug delivery system; Fluoroquinolone; Osteomyelitis; Poly(methylmethacrylate).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology
  • Biocompatible Materials / chemistry*
  • Bone Cements / chemistry*
  • Calcium Phosphates / chemistry*
  • Drug Carriers / chemistry
  • Drug Delivery Systems / methods
  • Levofloxacin / chemistry*
  • Levofloxacin / pharmacology
  • Materials Testing / methods
  • Microbial Sensitivity Tests / methods
  • Polymethyl Methacrylate / chemistry*
  • Porosity
  • Staphylococcus aureus / drug effects
  • Staphylococcus epidermidis / drug effects

Substances

  • Anti-Bacterial Agents
  • Biocompatible Materials
  • Bone Cements
  • Calcium Phosphates
  • Drug Carriers
  • Levofloxacin
  • Polymethyl Methacrylate
  • calcium phosphate