Pulmonary delivery for the treatment of tuberculosis

• Main Author: Poh, Wilson Kwok Choon
• Other Authors: Loo Say Chye Joachim
• Format: Thesis-Doctor of Philosophy
• Language: English
• Published: Nanyang Technological University 2020
• Subjects: Engineering::Materials::Biomaterials
• Online Access: https://hdl.handle.net/10356/137335
• Institution: Nanyang Technological University

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 taxes 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 favourable therapy. It is 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 (SPIOs), into a 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 are shown to be magnetically susceptible in an in-vitro assessment, viable against A549 epithelial cells, and are able to reduce two log bacteria counts of the BCG organism. Furthermore, through the use of an external magnet, our in-silico Computational Fluid Dynamics (CFD) simulations support the notion of yielding close to a 100% deposition in the deep lungs. Our proposed inhalation therapy circumvents challenges related to oral and respiratory treatments and embodies a highly favourable new treatment regime.