Development and characterization of nitazoxanide-loaded poly(ε-caprolactone) membrane for GTR/GBR applications

Dent Mater. 2024 Dec;40(12):2164-2172. doi: 10.1016/j.dental.2024.10.007. Epub 2024 Oct 22.

Abstract

Objective: Guided tissue/guided bone regeneration (GTR/GBR) membranes are widely used for periodontal bone regeneration, but their success depends on a bacteria-free environment. Systemic antibiotic treatment often proves inadequate, moreover, the increasing prevalence of antibiotic resistance in oral infections exacerbates this challenge. This study aimed to fabricate antibacterial membranes using a new class of antibiotics for local drug delivery, to eradicate infections and promote tissue regeneration.

Methods: Membranes loaded with nitazoxanide (NTZ) were fabricated via electrospinning using poly(ε-caprolactone) (PCL) with varying concentrations of NTZ (0 %, 2.5 %, and 5 % w/w) relative to the polymer weight. Morphochemical of NTZ-loaded membranes were assessed using scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS) and Fourier Transform Infrared spectroscopy (FTIR). Mechanical properties were evaluated using universal testing machine and NTZ release profile from membranes was determined by spectrophotometer (λmax = 444) for 14 days. Antimicrobial efficacy against periodontal pathogens, cell compatibility and mineralization were evaluated using periodontal ligament stem cells (PDLSCs).

Results: Optimized spinning parameter maintained a uniform fiber diameter and successful loading of NTZ was confirmed by SEM-EDS and FTIR. NTZ incorporation did not significantly affect mechanical properties, whereas the drug release kinetics showed an initial burst, followed by sustained release over 14 days. NTZ-loaded membranes demonstrated antibacterial activity against Aggregatibacter actinomycetemcomitans (Aa) and Fusobacterium nucleatum (Fn). Importantly, the presence of NTZ showed minimal cell toxicity; however, it reduced the mineralization potential compared with that of the pure PCL membrane, which increased over time.

Significance: Taken together, these findings established that NTZ-loaded membranes could be promising barrier membrane to counteract microbial environment and aid periodontal bone regeneration.

Keywords: Antimicrobial; Bone; Drug Release; Electrospinning; Nitazoxanide; Periodontitis.

MeSH terms

  • Aggregatibacter actinomycetemcomitans / drug effects
  • Anti-Bacterial Agents* / chemistry
  • Anti-Bacterial Agents* / pharmacology
  • Bone Regeneration / drug effects
  • Fusobacterium nucleatum / drug effects
  • Guided Tissue Regeneration, Periodontal / methods
  • Humans
  • Materials Testing
  • Membranes, Artificial*
  • Microscopy, Electron, Scanning*
  • Nitro Compounds* / chemistry
  • Polyesters* / chemistry
  • Spectrometry, X-Ray Emission
  • Spectroscopy, Fourier Transform Infrared
  • Surface Properties
  • Thiazoles*

Substances

  • polycaprolactone
  • Polyesters
  • Thiazoles
  • Anti-Bacterial Agents
  • Membranes, Artificial
  • nitazoxanide
  • Nitro Compounds