Dopamine-assisted fixation of drug-loaded polymeric multilayers to osteoarticular implants for tuberculosis therapy

Biomater Sci. 2017 Mar 28;5(4):730-740. doi: 10.1039/c7bm00042a.

Abstract

Currently, the major issues in the treatment of osteoarticular tuberculosis (TB) after implant placement are low drug concentration at the infected focus and drug resistance resulting from the long-term chemotherapy. The application of drug-loaded polymeric multilayers on implantable devices offers a promising solution to the problems. Herein, a poly(ethylene glycol)-based hydrogel film embedded with isoniazid (INH)-loaded alginate microparticles was fixed to Ti implants via adhesive polydopamine, subsequently capped by poly(lactic-co-glycolic acid) membranes for the sustained and localized delivery of the anti-TB drug. The antibacterial efficacy of the released INH was confirmed by a 4.5 ± 0.8 cm inhibition zone formed in the fourth week after inoculation of Mycobacterium tuberculosis. The INH-loaded Ti implants showed no toxicity to the osteoblast cell and provided a consistent drug release for nearly one week in vitro. The release profile in vivo showed a high local concentration and low systemic exposure. The local INH concentration could be kept higher than its minimum inhibitory concentration over a period of 8 weeks, which proves that it is a promising strategy to improve the severe osteoarticular TB treatment.

MeSH terms

  • Adhesives / chemistry*
  • Animals
  • Antitubercular Agents / administration & dosage*
  • Antitubercular Agents / therapeutic use
  • Cell Line
  • Drug Delivery Systems / methods*
  • Drug Liberation
  • Female
  • Humans
  • Indoles / chemistry*
  • Isoniazid / administration & dosage*
  • Isoniazid / therapeutic use
  • Lactic Acid / chemistry
  • Male
  • Mice
  • Mycobacterium tuberculosis / drug effects
  • Polyethylene Glycols / chemistry*
  • Polyglycolic Acid / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polymers / chemistry*
  • Prostheses and Implants
  • Rabbits
  • Tuberculosis, Osteoarticular / drug therapy*
  • Tuberculosis, Osteoarticular / microbiology

Substances

  • Adhesives
  • Antitubercular Agents
  • Indoles
  • Polymers
  • polydopamine
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Polyethylene Glycols
  • Isoniazid