Preparation, characterization, and in vitro cytotoxicity evaluation of a novel anti-tuberculosis reconstruction implant

PLoS One. 2014 Apr 16;9(4):e94937. doi: 10.1371/journal.pone.0094937. eCollection 2014.

Abstract

Background: Reconstruction materials currently used in clinical for osteoarticular tuberculosis (TB) are unsatisfactory due to a variety of reasons. Rifampicin (RFP) is a well-known and highly effective first-line anti-tuberculosis (anti-TB) drug. Poly-DL-lactide (PDLLA) and nano-hydroxyapatite (nHA) are two promising materials that have been used both for orthopedic reconstruction and as carriers for drug release. In this study we report the development of a novel anti-TB implant for osteoarticular TB reconstruction using a combination of RFP, PDLLA and nHA.

Methods: RFP, PDLLA and nHA were used as starting materials to produce a novel anti-TB activity implant by the solvent evaporation method. After manufacture, the implant was characterized and its biodegradation and drug release profile were tested. The in vitro cytotoxicity of the implant was also evaluated in pre-osteoblast MC3T3-E1 cells using multiple methodologies.

Results: A RFP/PDLLA/nHA composite was successfully synthesized using the solvent evaporation method. The composite has a loose and porous structure with evenly distributed pores. The production process was steady and no chemical reaction occurred as proved by Fourier Transform Infrared Spectroscopy (FTIR) and X-Ray Diffraction (XRD). Meanwhile, the composite blocks degraded and released drug for at least 12 weeks. Evaluation of in vitro cytotoxicity in MC3T3-E1 cells verified that the synthesized composite blocks did not affect cell growth and proliferation.

Conclusion: It is feasible to manufacture a novel bioactive anti-TB RFP/PDLLA/nHA composite by the solvent evaporation method. The composite blocks showed appropriate properties such as degradation, drug release and biosafety to MC3T3-E1 cells. In conclusion, the novel composite blocks may have great potential for clinical applications in repairing bone defects caused by osteoarticular TB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antitubercular Agents / chemistry
  • Antitubercular Agents / pharmacokinetics
  • Antitubercular Agents / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Drug Compounding / methods
  • Drug Implants*
  • Durapatite / chemistry
  • Durapatite / pharmacokinetics
  • Durapatite / pharmacology*
  • Mice
  • Microscopy, Electron, Scanning
  • Nanocomposites / chemistry
  • Nanocomposites / ultrastructure
  • Osteoblasts / cytology
  • Osteoblasts / drug effects
  • Polyesters / chemistry
  • Polyesters / pharmacokinetics
  • Polyesters / pharmacology*
  • Porosity
  • Rifampin / chemistry
  • Rifampin / pharmacokinetics
  • Rifampin / pharmacology*
  • Spectroscopy, Fourier Transform Infrared
  • Tuberculosis, Osteoarticular / drug therapy
  • X-Ray Diffraction

Substances

  • Antitubercular Agents
  • Drug Implants
  • Polyesters
  • poly(lactide)
  • Durapatite
  • Rifampin

Grants and funding

This project was supported in part by the National Basic Research Program of China (973 Program, 2012CB933601). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.