Bacterial infections are still one of the major concerns of global public health, especially due to the increasing cases of antibiotic resistant bacteria. Since the research for new antibacterial compounds is not generating enough valid alternatives, new approaches must be evaluated. For this reason, a combinational approach that can increase both the delivery and the potency of the classical antibiotics while, at the same time, minimise the side effects was studied in this work. To achieve this, the antibiotics were linked to biomimetic magnetic nanoparticles that can allow accumulation at the target site and the combination with other treatments, like in this case the magnetic hyperthermia. The process of functionalization of the magnetic nanoparticles with four antibiotics (ampicillin, tetracycline, gentamicin and ciprofloxacin) was studied. The nanoassemblies physical properties, binding efficiency and stability were analysed to ensure a suitable carrier. Moreover, they were tested against Gram-positive and Gram-negative bacteria, both with and without the application of magnetic hyperthermia to see their effects. At the end it was possible to demonstrate that the magnetic nanoparticles can be successfully functionalized with the antibiotics and that their bond is stable. Incomplete release of the antibiotic even under hyperthermia conditions prevented an effect when the functionalized antibiotic was set at the minimal inhibitory concentration. Thus, a clear synergistic effect was not detectable and further studies with increased antibiotic concentrations will be required.
Le infezioni batteriche continuano ad essere una delle maggiori preoccupazioni riguardanti la salute pubblica a livello globale, soprattutto a causa dell’aumento dei casi di antibiotico-resistenza. Poiché la ricerca di nuovi composti con proprietà antibatteriche non sta generando sufficienti alternative valide, devono essere valutati nuovi approcci. Per questo motivo, in questo lavoro è stato studiato un approccio combinato che possa aumentare sia il rilascio che la potenza dei classici antibiotici e allo stesso tempo minimizzare gli effetti collaterali. Per realizzare questo progetto degli antibiotici sono stati legati a delle nanoparticelle magnetiche biomimetiche che ne permettono l’accumulo nel sito target e la possibilità di essere combinate con altri trattamenti, ad esempio l’ipertermia magnetica. È stato studiato il processo di funzionalizzazione delle nanoparticelle magnetiche con quattro antibiotici (ampicillina, tetraciclina, gentamicina e ciprofloxacina). Per confermare l’adeguatezza dei carrier sono state analizzate le proprietà fisiche, l’efficienza e la stabilità del legame tra gli antibiotici e le nanoparticelle. Inoltre, questi carrier sono stati testati contro batteri Gram-positivi e Gram-negativi, sia con che senza l’esposizione al trattamento di ipertermia magnetica per osservare il loro comportamento. Alla fine, è stato possibile dimostrare che le nanoparticelle magnetiche possono essere funzionalizzate con successo con gli antibiotici e che il loro legame con essi è stabile. Utilizzando le nanoparticelle funzionalizzate alla concentrazione inibitoria minima, il rilascio incompleto di antibiotico, anche in condizioni di ipertermia, ha impedito un effetto. Di conseguenza, non è stato possibile rilevare un chiaro effetto sinergico e saranno necessari studi futuri con una maggiore concentrazione di antibiotico.
Characterization of antibiotic nanoassemblies with magnetic nanoparticles and evaluation of their behaviour with magnetic hyperthermia
ZERBETTO, SOFIA
2022/2023
Abstract
Bacterial infections are still one of the major concerns of global public health, especially due to the increasing cases of antibiotic resistant bacteria. Since the research for new antibacterial compounds is not generating enough valid alternatives, new approaches must be evaluated. For this reason, a combinational approach that can increase both the delivery and the potency of the classical antibiotics while, at the same time, minimise the side effects was studied in this work. To achieve this, the antibiotics were linked to biomimetic magnetic nanoparticles that can allow accumulation at the target site and the combination with other treatments, like in this case the magnetic hyperthermia. The process of functionalization of the magnetic nanoparticles with four antibiotics (ampicillin, tetracycline, gentamicin and ciprofloxacin) was studied. The nanoassemblies physical properties, binding efficiency and stability were analysed to ensure a suitable carrier. Moreover, they were tested against Gram-positive and Gram-negative bacteria, both with and without the application of magnetic hyperthermia to see their effects. At the end it was possible to demonstrate that the magnetic nanoparticles can be successfully functionalized with the antibiotics and that their bond is stable. Incomplete release of the antibiotic even under hyperthermia conditions prevented an effect when the functionalized antibiotic was set at the minimal inhibitory concentration. Thus, a clear synergistic effect was not detectable and further studies with increased antibiotic concentrations will be required.File | Dimensione | Formato | |
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https://hdl.handle.net/20.500.12608/61190