BIO Fe-antibiotic Hydrogels as a Novel Antibiotic Treatment against Gram-Negative Bacteria

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From the knowledge I have gained from my degree and additional work, I hope to conduct research into the generation and application of substances with the potential to act as nanoantibiotics. Nanomaterials, such as silver (Ag), have already been used in wound dressings and as linings in reusable shopping bags due to their antimicrobial properties, whilst nanomaterials in general are thought to use different mechanisms in order to inflict bacterial death. Ag is just one nanomaterial which is known to have these characteristics, although others, such as copper, zinc oxide, titanium and silica, are also considered to share this exploitable feature. It has also been suggested that nanomaterials may have lower toxicity levels associated with their use, in comparison to other novel therapies also considered to be future antibacterial alternatives. In considering this, nanomaterials' clinical usage could be more favourable than other substances which could have more severe off- target toxicities.The antibacterial properties possessed by nanomaterials make them an attractive alternative to the clinical (and potentially environmental) use of antibiotics. My intention is to compare the antibacterial activity and tendencies of standard antibiotics to nanomaterials (those previously described as being antibacterial) and nanomaterials conjugated with iron (Fe). Fe is an essential micronutrient which bacteria require to be pathogenic (that being disease-causing) and in order to make more bacterial progeny. By conjugating each nanomaterial with Fe there is the potential to increase nanomaterial delivery to bacteria alongside possible enhanced antibacterial effect. The concept of this project focusses on using the nanomaterial-Fe conjugations to target bacteria currently considered the most problematic to humans; those with several known antibiotic resistances.For a novel therapy to eventually be used clinically, it is important to understand the effects which substances might have on the human system. This project aims to take this into account, by incorporating mammalian cells into experiments. This is crucial to involve in order to gain insight into potential side effects associated with toxicity, providing meaningful conclusions, those which are relevant physiologically, to be made concerning their future clinical use. Moreover, by using a cell line, such as Caco-2 cells, this will reduce the requirement for animals in research which can be wasteful and unethical in addition to not requiring Home Office approval which would be required for use of animals and also experimentation on primary cells.By investigating the minimum inhibitory concentration (MIC) (the lowest concentration of a substance required to stop bacterial growth), this can give an indication of the efficacy of each treatment condition (antibiotic, nanomaterial alone or nanomaterial-Fe conjugation). It would be expected that bacteria with known resistances would have a lower MIC when treated with nanomaterial and nanomaterial-Fe conjugation, in comparison to antibiotic if the nanomaterials are able to exert their antibacterial properties. Whilst, nanomaterial-Fe conjugation may aide the delivery of nanomaterial to bacteria, as these organisms have several mechanisms aiding the uptake and movement of Fe from the bacterium's external environment, across the cell envelope, and into the internal region of the cell, the periplasm.