A new multifunctionalized material against multi-drug resistant bacteria and abnormal osteoclast activity

Eur J Pharm Biopharm. 2018 Jun:127:120-129. doi: 10.1016/j.ejpb.2018.02.018. Epub 2018 Feb 15.

Abstract

The development of new biomaterials able to favor bone formation and to inhibit bone abnormal resorption is mandatory to face the increasing number of age-related musculo-skeletal disorders. Moreover, the increasing antibiotic resistance of clinically important bacteria, which is among the main causes of implant failure, requires new antimicrobial systems. In this study, we prepared multifunctional materials consisting of hydroxyapatite-zoledronate composite crystals decorated with Ag Nanoparticles (AgNPs). Zoledronate, a potent bisphosphonate widely applied for the treatment of pathologies associated to abnormal bone loss, was incorporated into hydroxyapatite up to about 8 wt%. Loading of poly(ethylenimine) - stabilized AgNPs onto the crystals was promoted by zoledronate functionalization and provoked a significant variation of the values of zeta potential. The results of in vitro tests demonstrate that the multifunctional materials combine the beneficial actions of zoledronate and AgNPs. In fact, they improve osteoblast differentiation and activity, whereas they inhibit osteoclastogenesis and osteoclast differentiation, and significantly hinder the growth of multi-drug resistant Gram positive and Gram negative bacteria. As a consequence, they can be exploited both as antiresorptive agents and as antimicrobial materials able to prevent the development of bone-associated infections.

Keywords: Bisphosphonate; Hydroxyapatite; Multi-drug resistant bacteria; Osteoblast/osteoclast co-cultures; Osteoporosis; Silver nanoparticles; Zoledronate.

MeSH terms

  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology*
  • Biocompatible Materials / chemistry
  • Cell Differentiation / drug effects
  • Cell Line
  • Diphosphonates / chemistry
  • Diphosphonates / pharmacology
  • Drug Resistance, Multiple, Bacterial / drug effects*
  • Gram-Negative Bacteria / drug effects
  • Humans
  • Imidazoles / chemistry
  • Imidazoles / pharmacology
  • Metal Nanoparticles / chemistry*
  • Microbial Sensitivity Tests / methods
  • Osteoblasts / drug effects
  • Osteoclasts / drug effects*
  • Silver / chemistry*
  • Zoledronic Acid

Substances

  • Anti-Bacterial Agents
  • Biocompatible Materials
  • Diphosphonates
  • Imidazoles
  • Silver
  • Zoledronic Acid