Tobramycin Supplemented Small-Diameter Vascular Grafts for Local Antibiotic Delivery: A Preliminary Formulation Study

Int J Mol Sci. 2021 Dec 17;22(24):13557. doi: 10.3390/ijms222413557.

Abstract

Peripheral artery occlusive disease is an emerging cardiovascular disease characterized by the blockage of blood vessels in the limbs and is associated with dysfunction, gangrene, amputation, and a high mortality risk. Possible treatments involve by-pass surgery using autologous vessel grafts, because of the lack of suitable synthetic small-diameter vascular prosthesis. One to five percent of patients experience vascular graft infection, with a high risk of haemorrhage, spreading of the infection, amputation and even death. In this work, an infection-proof vascular graft prototype was designed and manufactured by electrospinning 12.5% w/v poly-L-lactic-co-glycolic acid solution in 75% v/v dichloromethane, 23.8% v/v dimethylformamide and 1.2% v/v water, loaded with 0.2% w/wPLGA. Polymer and tobramycin concentrations were selected after viscosity and surface tension and after HPLC-UV encapsulation efficiency (EE%) evaluation, respectively. The final drug-loaded prototype had an EE% of 95.58% ± 3.14%, with smooth fibres in the nanometer range and good porosity; graft wall thickness was 291 ± 20.82 μm and its internal diameter was 2.61 ± 0.05 mm. The graft's antimicrobic activity evaluation through time-kill assays demonstrated a significant and strong antibacterial activity over 5 days against Staphylococcus aureus and Escherichia coli. An indirect cell viability assay on Normal Human Dermal Fibroblasts (NHDF) confirmed the cytocompatibility of the grafts.

Keywords: electrospinning; local drug delivery; microbicidal effect; small-diameter vascular graft; tobramycin.

MeSH terms

  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Blood Vessel Prosthesis*
  • Drug Carriers / chemistry
  • Drug Delivery Systems* / instrumentation
  • Drug Liberation
  • Escherichia coli / drug effects
  • Escherichia coli Infections / drug therapy
  • Humans
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemistry
  • Staphylococcal Infections / prevention & control
  • Staphylococcus aureus / drug effects
  • Tobramycin / administration & dosage*
  • Tobramycin / chemistry
  • Tobramycin / pharmacology
  • Vascular Grafting

Substances

  • Anti-Bacterial Agents
  • Drug Carriers
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Tobramycin