Construction of a highly potent inhalable microparticles combination therapy to treat pulmonary tuberculosis
File(s)
Author(s)
Alzahabi, Khaled
Type
Thesis
Abstract
Active tuberculosis (TB) is treated orally by a combination of many anti-TB drugs for a minimum of 6 months. Lengthy treatment and side effects of anti-TB drugs along with their poor delivery to the lungs following oral delivery affect patients’ adherence to the treatment. The aim was to design targeted and effective therapy to shorten the treatment period and improve patient adherence. The main challenge, which was achieved, was to combine Rifampicin (RIF) and Isoniazid (INH), due to their different hydrophilicity, in respirable microparticles that carry silver nanoparticles (AgNPs; antibacterial agent synthesized by bath reduction method to increase the anti-TB drugs potency) to treat TB via inhalation therapy. AgNPs were spherical, with a mean diameter of 15-18 nm. 10 µg/ml of AgNPs in serum free medium were not toxic when applied to different human lung cells for 72 h. PLGA microparticles containing AgNPs, RIF and INH exhibited a spherical-donut shape with a geometric and aerodynamic diameter of less than 6 µm and both drugs were successfully encapsulated with a ratio of 1.5:10 (Drugs: PLGA). The PLGA microparticles loaded with AgNPs, INH and RIF did not affect the metabolic activity of the exposed-cells at doses of less than 1.562, 6.25 and 12.5 µg/ml, respectively. 0.0031, 0.0125, 0.025 µg/ml of AgNPs, INH and RIF, respectively, loaded within PLGA microparticles inhibited BCG growth with lower doses of RIF and INH in comparison to the combined therapy with RIF and INH (0.03 µg/ml of each)...
Version
Open Access
Date Issued
2023-09-07
Date Awarded
01/12/2023
License URL
Advisor
Tetley, Terry
Porter, Alexandra
Sponsor
Imperial College London
Engineering and Physical Sciences Research Council
Grant Number
CIVG_G01463
Publisher Department
Materials
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)