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Novel nanoparticle formulations for antimicrobial action

Al-Mamoori, Ahmed Fawzi Halbus


Ahmed Fawzi Halbus Al-Mamoori


Vesselin N. Paunov

Tommy S. Horozov


Colloidal particles are being extensively studied in various antimicrobial applications due to their small size, enormous surface area to volume ratio and ability to exhibit a wide spectrum of antibacterial, antifungal, antialgal and antiviral action. This thesis aims to develop novel nanoparticle formulations for antimicrobial action. The present work focuses on various nanoparticles (NPs) of inorganic materials and discusses some of the methods for their preparation as well as mechanisms of their antimicrobial action. The antimicrobial applications of metal oxide nanoparticles (zinc oxide and copper oxide) and metal hydroxide nanoparticles such as magnesium hydroxide were studied. Recent advances in the functionalization of nanoparticles and their potential antimicrobial applications were also studied as a viable alternative of conventional antibiotics and antiseptic agents which can help to tackle antimicrobial resistance.

The synthesis and characterisation of a range of surface modified zinc oxide (ZnONPs, Chapter 3 and 4), magnesium hydroxide Mg(OH)2NPs (Chapter 5 and 6) and copper oxide (CuONPs, Chapter 7 and 8) have been described including particle size distribution, crystallite size, zeta potential, isoelectric point, X-ray diffraction (XRD), dynamic light scattering (DLS), scanning electron microscopy (SEM), etc. The antibacterial, anti-algal and anti-yeast activity of the modified nanoparticles on microalgae (C. reinhardtii), yeast (S. cerevisiae) and Escherichia coli (E.coli) were explored. The viability of these cells was evaluated for various concentrations and exposure times with nanoparticles. It was discovered that the antimicrobial activity of uncoated nanoparticles on the viability of C. reinhardtii occurred at considerably lower particle concentrations than for S. cerevisiae and E.coli. The results indicate that the antimicrobial activity of polyelectrolyte-coated nanoparticles alternates with their surface charge. The anionic nanoparticles (ZnONPs/PSS, ZnONPs/ZnS, ZnONPs/SiO2, CuONPs/PSS and Mg(OH)2NPs/PSS) have much lower antibacterial activity than the cationic ones (NPs/PSS/PAH and uncoated NPs). These findings have been explained by the lower adhesion of the anionic nanoparticles to the cell wall because of electrostatic repulsion and the enhanced particle-cell adhesion due to electrostatic attraction in the case of cationic nanoparticles. The results can potentially be applied to control the cytotoxicity and the antimicrobial activity of other inorganic nanoparticles.

A novel type of antimicrobial formulation of CuONPs has been developed and tested. This has been achieved by functionalizing CuONPs with (3-glycidyloxypropyl)- trimethoxysilane (GLYMO) and subsequent covalent coupling of 4- hydroxyphenylboronic acid (4-HPBA). As the boronic acid (BA) groups on the surface of CuONPs/GLYMO/4-HPBA can form reversible covalent bonds with the diol groups of glycoproteins on the bacterial cell surface, they can strongly bind to the cells walls resulting in a very strong enhancement of their antibacterial, anti-algal and anti-yeast action which is not based on electrostatic adhesion. This work (Chapter 8) demonstrates that the CuONPs with boronic acid surface functionality are far superior antibacterial agents compared to bare CuONPs. The results showed that the antibacterial, anti-algal and anti-yeast impact of the 4-HPBA-functionalized CuONPs on Rhodococcus rhodochrous (R. rhodochrous), E.coli, C. reinhardtii and S. cerevisiae is one order of magnitude higher than that of bare CuONPs or CuONPs/GLYMO. It was also observed a marked increase of the 4-HPBA-functionalized CuONPs antibacterial action on these microorganisms at shorter incubation times compared with the bare CuONPs at the same conditions. Significantly, the results show that the cytotoxicity of CuONPs functionalized with 4-HPBA as an outer layer can be controlled by the concentration of glucose in the media, and that the effect is reversible as glucose competes with the sugar residues on the bacterial cell walls for the BA-groups on the CuONPs. The experiments with human keratinocyte cell line exposure to CuONPs/GLYMO/4-HPBA indicated lack of measurable cytotoxicity at particle concentrations which are effective as an antibacterial agent for both R. rhodochrous, E. coli, C. reinhardtii and S. cerevisiae. This suggests that formulations of CuONPs/GLYMO/4-HPBA can be used to drastically reduce the overall CuO concentration in antimicrobial formulations while strongly increasing their efficiency.

The role of surface roughness in the antimicrobial activity of oxide nanoparticles has been studied (Chapter 9). This has been achieved by comparing the antimicrobial action of non-porous silica nanoparticles (SiO2NPs) with smooth surface and mesoporous surfacerough SiO2NPs, both functionalized with GLYMO and 4-HPBA. Surface-rough mesoporous silica nanoparticles (‘ghost’ SiO2NPs) have been fabricated by using composite mesoporous copper oxide nanoparticles (‘host’ CuONPs) as templates which allowed the SiO2NPs to copy their surface morphology. It was demonstrated that the functionalized ‘ghost’ SiO2NPs with GLYMO and 4-HPBA (SiO2NPs/GLYMO/4-HPBA) show a very significant antibacterial effect compared to smooth SiO2NPs of the same surface coating and particle size. This was attributed to the ‘ghost’ SiO2NPs surface morphology which mimics to certain extent the surface of the original CuONPs used as templates for their preparation. It can be envisaged that the ‘ghost’ SiO2NPs effectively acquire some of the antibacterial properties from the ‘host’ CuONPs, with the same functionality, despite being completely free of copper. Antibacterial tests showed that the ‘ghost’ SiO2NPs/GLYMO/4-HPBA have much higher antibacterial action than the nonfunctionalized ‘ghost’ SiO2NPs or GLYMO functionalized ‘ghost’ SiO2NPs for R. rhodochrous. The results indicate that the combination of rough surface morphology and strong adhesion of the particle surface to the bacteria can make even benign material as silica act as a strong antimicrobial.


Al-Mamoori, A. F. H. (2019). Novel nanoparticle formulations for antimicrobial action. (Thesis). University of Hull. Retrieved from

Thesis Type Thesis
Deposit Date Sep 1, 2022
Publicly Available Date Feb 24, 2023
Keywords Chemistry
Public URL
Additional Information Department of Chemistry and Biochemistry, The University of Hull
Award Date Jun 1, 2019


Thesis (29.7 Mb)

Copyright Statement
© 2019 Al-Mamoori, Ahmed Fawzi Halbus. All rights reserved. No part of this publication may be reproduced without the written permission of the copyright holder.

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