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Drug Delivery and Translational Research

, Volume 9, Issue 1, pp 97–105 | Cite as

Development and biological evaluation of a new nanotheranostic for tuberculosis

  • Edward Helal-Neto
  • Suyene Rocha Pinto
  • Filipe Leal Portilho
  • Marcellus Dias da Costa
  • Jonathas Xavier Pereira
  • Fiammetta Nigro
  • Eduardo Ricci-Junior
  • Andre Luis Peixoto Candéa
  • Maria das Graças Muller de Oliveira Henriques
  • Ralph Santos-OliveiraEmail author
Original Article

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

Radiopharmaceuticals Nanotechnology Smart device Infection 

Abbreviations

TB

Tuberculosis

BK

Koch’s bacillus

99mTc

Technetium 99 metastable

SPECT

Single-photon emission computed tomography

mCi

Milli Curie

MBq

Mega Becquerel

RPMI

Roswell Park Memorial Institute medium

PVA

Polyvinyl alcohol

PCL

Polycaprolactone

DLS

Dynamic light scattering

SEM

Scanning electron microscopy

NIH

National Institutes of Health

BCG

Bacillus Calmette–Guérin

CFU

Colony-forming units

PBS

Phosphate-buffered saline

PFA

Paraformaldehyde

EMB

Ethambutol

PDI

Polydispersity index

EPR

Enhanced permeability and retention

Notes

Funding

The authors would like to thank FAPERJ and CNPq for the financial support of this research.

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflicts of interest.

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Copyright information

© Controlled Release Society 2018

Authors and Affiliations

  • Edward Helal-Neto
    • 1
  • Suyene Rocha Pinto
    • 1
  • Filipe Leal Portilho
    • 1
  • Marcellus Dias da Costa
    • 2
  • Jonathas Xavier Pereira
    • 3
  • Fiammetta Nigro
    • 4
  • Eduardo Ricci-Junior
    • 4
  • Andre Luis Peixoto Candéa
    • 5
  • Maria das Graças Muller de Oliveira Henriques
    • 5
  • Ralph Santos-Oliveira
    • 1
    • 6
    Email author
  1. 1.Brazilian Nuclear Energy CommissionNuclear Engineering InstituteRio de JaneiroBrazil
  2. 2.Fiocruz FoundationNational Institute of InfectologyRio de JaneiroBrazil
  3. 3.Institute of Biomedical Science, Laboratory of Proliferation and Cell DifferentiationFederal University of Rio de JaneiroRio de JaneiroBrazil
  4. 4.College of Pharmacy, Galenical Development LaboratoryFederal University of Rio de JaneiroRio de JaneiroBrazil
  5. 5.Laboratory of Applied Pharmacology, FarmanguinhosOswaldo Cruz FoundationRio de JaneiroBrazil
  6. 6.Laboratory of Radiopharmacy and NanoradiopharmaceuticalsZona Oeste State UniversityRio de JaneiroBrazil

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