Dual delivery of active antibactericidal agents and bone morphogenetic protein at sustainable high concentrations using biodegradable sheath-core-structured drug-eluting nanofibers

Int J Nanomedicine. 2016 Aug 17:11:3927-37. doi: 10.2147/IJN.S107250. eCollection 2016.

Abstract

In this study, we developed biodegradable sheath-core-structured drug-eluting nanofibers for sustainable delivery of antibiotics (vancomycin and ceftazidime) and recombinant human bone morphogenetic protein (rhBMP-2) via electrospinning. To prepare the biodegradable sheath-core nanofibers, we first prepared solutions of poly(d,l)-lactide-co-glycolide, vancomycin, and ceftazidime in 1,1,1,3,3,3-hexafluoro-2-propanol and rhBMP-2 in phosphate-buffered solution. The poly(d,l)-lactide-co-glycolide/antibiotics and rhBMP-2 solutions were then fed into two different capillary tubes controlled by two independent pumps for coaxial electrospinning. The electrospun nanofiber morphology was observed under a scanning electron microscope. We further characterized the in vitro antibiotic release from the nanofibers via high-performance liquid chromatography and that of rhBMP-2 via enzyme-linked immunosorbent assay and alkaline phosphatase activity. We showed that the biodegradable coaxially electrospun nanofibers could release high vancomycin/ceftazidime concentrations (well above the minimum inhibition concentration [MIC]90) and rhBMP-2 for >4 weeks. These experimental results demonstrate that novel biodegradable nanofibers can be constructed with various pharmaceuticals and proteins for long-term drug deliveries.

Keywords: biodegradable sheath-core nanofibers; ceftazidime; coaxial electrospinning; release characteristics; rhBMP-2; vancomycin.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Biocompatible Materials / chemistry*
  • Bone Morphogenetic Protein 2 / pharmacology*
  • Ceftazidime / pharmacology
  • Drug Delivery Systems*
  • Drug Liberation
  • Humans
  • Lactic Acid / chemistry*
  • Microbial Sensitivity Tests
  • Nanofibers / chemistry*
  • Nanofibers / ultrastructure
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Rats, Sprague-Dawley
  • Spectroscopy, Fourier Transform Infrared
  • Tensile Strength
  • Vancomycin / pharmacology
  • Water / chemistry

Substances

  • Anti-Bacterial Agents
  • Biocompatible Materials
  • Bone Morphogenetic Protein 2
  • Water
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Vancomycin
  • Ceftazidime