Development and Biological Evaluation of a New Nanotheranostic for Tuberculosis

Drug Deliv Transl Res. 2019 Feb;9(1):97-105. doi: 10.1007/s13346-018-0577-6.

Abstract

In this study, we developed, characterized, and tested in vivo polymeric nanoparticle of ethambutol labeled with 99mTc as nanoradiopharmaceutical for early diagnosis of tuberculosis by single-photon emission computed tomography, also as a therapeutic choice. Nanoparticles were developed by double emulsification. All characterization tests were performed, as scanning electron microscopy and dynamic light scattering. The labeling process with 99mTc was performed using the direct labeling process. In vitro and in vivo assays were performed with animals and cells. The results showed that a spherical ethambutol nanoparticle with a size range of 280-300 nm was obtained. The stability test showed that the nanoparticles were well labeled with 99mTc (> 99.1%) and keep labeled over 24 h. The biodistribution assay showed that almost 18% of the nanoparticles were uptake by the lung in infected mice (male C57Bl/6) with Mycobacterium bovis BCG (4 × 105 CFU/cavity), corroborating its use as a nanodrug for tuberculosis imaging. The results for the cell assay corroborate its therapeutical effect. We developed and efficiently tested a new nanodrug that can be used for both imaging and therapy of tuberculosis, acting as a novel nanotheranostic.

Keywords: Infection; Nanotechnology; Radiopharmaceuticals; Smart device.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antitubercular Agents / administration & dosage*
  • Antitubercular Agents / chemistry
  • Antitubercular Agents / pharmacokinetics
  • Dynamic Light Scattering
  • Ethambutol / administration & dosage*
  • Ethambutol / chemistry
  • Ethambutol / pharmacokinetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Electron, Scanning
  • Mycobacterium bovis / drug effects
  • Mycobacterium bovis / pathogenicity
  • Nanoparticles
  • Particle Size
  • Polymers
  • Radiopharmaceuticals / chemistry*
  • Radiopharmaceuticals / pharmacokinetics
  • Technetium / chemistry*
  • Technetium / pharmacokinetics
  • Tissue Distribution
  • Tomography, Emission-Computed, Single-Photon
  • Tuberculosis / diagnostic imaging*
  • Tuberculosis / drug therapy*
  • Tuberculosis / veterinary

Substances

  • Antitubercular Agents
  • Polymers
  • Radiopharmaceuticals
  • Technetium
  • Ethambutol