Active pulmonary targeting against tuberculosis (TB) via triple-encapsulation of Q203, bedaquiline and superparamagnetic iron oxides (SPIOs) in nanoparticle aggregates

Wilson Poh, Nurlilah Ab Rahman, Yan Ostrovski, Josue Sznitman, Kevin Pethe, Say Chye Joachim Loo

Research output: Contribution to journalArticlepeer-review

Abstract

Tuberculosis (TB) has gained attention over the past few decades by becoming one of the top ten leading causes of death worldwide. This infectious disease of the lungs is orally treated with a medicinal armamentarium. However, this route of administration passes through the body’s first-pass metabolism which reduces the drugs’ bioavailability and toxicates the liver and kidneys. Inhalation therapy represents an alternative to the oral route, but low deposition efficiencies of delivery devices such as nebulizers and dry powder inhalers render it challenging as a favorable therapy. It was hypothesized that by encapsulating two potent TB-agents, i.e. Q203 and bedaquiline, that inhibit the oxidative phosphorylation of the bacteria together with a magnetic targeting component, superparamagnetic iron oxides, into a poly (D, L-lactide-co-glycolide) (PDLG) carrier using a single emulsion technique, the treatment of TB can be a better therapeutic alternative. This simple fabrication method achieved a homogenous distribution of 500 nm particles with a magnetic saturation of 28 emu/g. Such particles were shown to be magnetically susceptible in an in-vitro assessment, viable against A549 epithelial cells, and were able to reduce two log bacteria counts of the Bacillus Calmette-Guerin (BCG) organism. Furthermore, through the use of an external magnet, our in-silico Computational Fluid Dynamics (CFD) simulations support the notion of yielding 100% deposition in the deep lungs. Our proposed inhalation therapy circumvents challenges related to oral and respiratory treatments and embodies a highly favorable new treatment regime.

Original languageEnglish
Pages (from-to)1039-1048
Number of pages10
JournalDrug Delivery
Volume26
Issue number1
DOIs
StatePublished - 1 Jan 2019

Keywords

  • Pulmonary drug delivery
  • computational fluid dynamics
  • nanoparticle aggregates
  • solvent emulsion
  • superparamagnetic iron oxides
  • tuberculosis

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

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