Mode of Action for Plant-Based Nanoparticles against Mycobacterium tuberculosis

5.7.1 Nanoparticles

Nanotechnology has been employed for the production of different materials at the nanoscale. It especially holds huge promise to improve human health, and it has been forecasted to be of tremendous benefits to humanity (Saravanan et al., 2018).

Nanoparticles are a wide class of materials that include particulate substances, which have one dimension less than 100 nm at least. There are several benefits to using nano-formulations for therapeutic uses, including lowering the dose of drug given to patients, resulting in less adverse reaction and perhaps decreasing the treatment time. This is made possible via enhanced sites-specific drug-bearing nanoparticle targeting resulting in increased drug concentration at the target site of interest while reducing delivery of drugs to non-target sites (Byrne et al., 2011). Nanoparticles possess large surface area compared to their volume, and their size is similar to that of macromolecules and organelles inside the cells like proteins and DNA. Interestingly, their small size allows macrophages to ingest and phagocytize them easily since macrophages ingest smaller objects or molecules more freely than do larger forms of the same material (Navalakhe and Nandedkar, 2007). Therefore, if drugs are in the nanoparticle form, it may be beneficial in treating some diseases such as ТВ and cancer (Clift et ah. 2008; Nasiruddin et ah, 2017).

5.7.2 Sugar Leakages

One of the mechanisms of antimicrobial effect of nanoparticles is the increase in cell membrane permeability of bacteria that can make cellular molecules, especially the sugar and protein, leak out of the cell (Gurunathan et ah, 2014). The effect of various applications of silver nanoparticles (AgNPs) have been seen in diagnostic biomarkers, cellular labels and drug delivery system for treatment of various diseases, especially infections and cancers. Silver nanoparticles have been extensively demonstrated to exhibit sugar leakage as one its mechanism of action. Rajesh et ah (2015) made a comment that the antimicrobial effect in using silver nanoparticles may probably be the sum of distinct mechanisms of action that include reaction of silver with thiol (SH) proteins. These altered protein groups inactivate the organism by inhibiting enzymes that are involved in the respiratory chains and thus interfere with permeability of protons and phosphate. This can generate reactive oxygen untreated control. His findings also demonstrated that silver nanoparticles as an antimicrobial involved the attachment to the cellular membrane, then enters the cytoplasm causing osmotic collapse and then release of intracellular contents that include sugar and protein. The ultimate result is cell death (Yuan et al., 2017). In a similar experiment conducted by Qayyum et al. (2017), the findings were of increased sugar and protein biomolecules after treating with silver nanoparticles, at two to three folds when compared to the sample that was untreated (control) (Qayyum et al., 2017).

5.7.3 Lipid Peroxidation

Peroxidation of lipid is known to take place commonly in the membrane of the cells and organelles due to their membrane composition. The commonest targets include unsaturated lipids and cholesterol. Common inducers of lipid peroxidation include the reactive oxygen species (ROS) such as hydroxyl radical, singlet oxygen and hydroperoxyl radical. Lipid peroxidation does not involve the damage of lipids alone, but also protein and nucleic acid. Several studies have showed that several metal oxide nanoparticles have the potential to exhibit spontaneous ROS production; this can cause the cell to enter the state of oxidative stress. If the cellular antioxidant defence is low, it can lead to the damage of cellular components of proteins, nucleic acid and lipids (Premanathan et al., 2011). The generation of the fatty acid from the breakdown of lipids can cause the activation of lipid peroxidase, which will initiate a chain reaction that will disrupt the membrane of organelles and cellular membrane. This can result in cell death (Premanathan et ah, 2011).

In the study investigating zinc oxide nanoparticles toxicity of prokaryotic and eukaryotic cells, antibacterial activity was tested and found that the nanoparticles with enhanced ultrasound induced lipid peroxidation in the liposomal membrane. The products of this lipid peroxidation were conjugated dienes, lipid hydroperoxides and malondialdehydes. The lipid peroxidation was a result of a chain reaction involving oxygen and mediated by free radicals. Zinc oxide nanoparticles were showed to enhance this process (Premanathan et ah, 2011).

Another study was conducted to examine the effectiveness of nanocrystalline TiO, with bromopyrogallol (Brp@Ti02) in photo-generating singlet oxygen, free radicals and also their ability to photosensitize peroxidation of unsaturated lipids. The result showed a type I mechanism of lipid peroxidation, which was indicated by the formation of free radicals dependent cholesterol oxidation products (Kozinska et ah, 2019).

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