Browsing by Author "Jaffer, Shaakirah"

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    Pro–apoptotic iron oxide nanosystems as selective anti – TB drugs
    (Stellenbosch : Stellenbosch University, 2024-03) Jaffer, Shaakirah; Malgas-Enus, Rehana; Mavumengwana, Vuyo; Stellenbosch University. Faculty of Science. Dept. of Chemistry and Polymer Science.
    ENGLISH ABSTRACT: Tuberculosis (TB) is reportedly the biggest airborne disease, after covid-19, and amongst the top 10 causes of death worldwide. The disease is mainly prevalent in low- and middle-income countries and has financial and social impacts that negatively affect development in these countries. Consequently, addressing the implications of this disease is highly important. According to the World Health Organization (WHO), approximately a third of the world’s population is infected with TB. TB is transmitted by inhaling a droplet of Mycobacterium tuberculosis (M. tuberculosis), it remains within the body as its latent form. However, it takes a weak immune system to activate the latent form to become active TB. With current treatments showing a moderate to high success rate, the duration of treatment which causes toxicity, and drug resistance are issues that are faced TB treatment. Treatment spans between 6 to 24 months depending on case severity, with accompanying acute side effects. Therefore, the purpose of this study was to investigate functionalized iron oxide nanoparticles and their efficacy as antimycobacterial agents. The synthesized bare iron oxide nanoparticles include magnetite (Fe3O4), ferrous oxide (FeO) and ferric oxide (Fe2O3) nanoparticles and were modified using compounds that are known to activate apoptosis including, 1,3,5-triaza-7-phosphaadamantane (PTA), 3,3′,3″-phosphanetriyltris (benzenesulfonic acid) trisodium salt (TPPTS), 9-β-D-arabinofuranosyl guanine hydrate (ara-g hydrate), 2,3-diphenylbenzo[g]quinoxaline-5,10-dione (DPBQ) and 4,5,6,7- tetrahydro-5,5,7,7-tetramethyl-2-[[(5-nitro-2-thienyl) carbonyl]amino]-thieno[2,3-c]pyridine-3- carboxylic acid ethyl ester (NPC -26). Characterization techniques included, fourier transform infrared spectroscopy (FT–IR), ultraviolet – visible spectroscopy (UV-Vis) and high-resolution transmission electron microscopy (HR-TEM) on the synthesized and modified nanoparticles. The selected bare nanoparticles and modified nanoparticles were tested for antimycobacterial activity against Mycobacterium smegmatis (M. smegmatis), frequently used to emulate M. tuberculosis due to its non-infectious attributes. Interestingly, both the bare and modified nanoparticles noticeably promoted growth of M. smegmatis in a dose dependent manner at all concentrations tested ranging from 250 to 1,95 µg/mL. A rapid uptake effect on iron oxide nanoparticles by M. smegmatis caused an exponential increase in bacterial growth, indicating that the bacterium itself was able to metabolize both the bare and modified nanoparticles synthesized in this study. The dose dependant results indicated a notable affinity of mycobacteria for the bare iron oxide nanoparticles, suggesting a high binding capability and implicating a potential role of iron acquisition mechanisms in the pathogenesis or survival strategies of mycobacteria. The iron oxide nano system that piqued interest was magnetite + NPC-26 which showed a degree of potential at the lowest concentration of 1,95 µg/mL. The dosage effect of this concentration showed a more progressive growth curve showing inhibition of the bacterial growth over the 5-day test period. Thus, the cells uptake of the magnetite was due to an affinity for iron and the NPC-26 inhibiting cell growth to some extent. The study set out to synthesize three variations of iron oxide nanoparticles with the intent to capitalize on the distinctive properties of iron oxide nanoparticles to allow for precise drug delivery to the site of infection. Further modifying the nanoparticles with apoptotic-inducing drugs to enhance the efficacy of treatment by promoting programmed cell death in infected cells and accelerating the clearance of the pathogen. The utilization of magnetite loaded with NPC-26 demonstrated a noteworthy inhibitory effect on the growth of mycobacteria, as indicated by the dosage effect experimental results. Therefore, the utilization of the iron oxide nanoparticles modified with apoptotic-inducing abilities may have significant promise as a novel and targeted approach for the treatment of tuberculosis.