Preventing infections in an ageing population: new nano/microcarriers for antibacterial coatings

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Ferreira, A.M., 2023. Preventing infections in an ageing population: new nano/microcarriers for antibacterial coatings. PhD, Nottingham Trent University.

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Abstract

Infection diseases are responsible for high mortality and morbidity in the elderly, with the treatment of a single resistant infection being extremely costly due to the extended hospitalization periods and additional treatment costs. Contaminated surfaces are associated with the spread of pathogenic microorganisms, being a dangerous transmission route in hospital settings, where the incidence of antimicrobial-resistant infections has reached alarming levels. Surfaces coated with antimicrobial agents have allowed the production of safe surfaces that can prevent the spread of microorganisms, with silver nanoparticles (AgNPs) being widely used due to their broad spectrum of bioactivity. Nevertheless, the colloidal instability of AgNPs and adverse effects on living organisms have driven the search for materials able to stabilize and control silver release. Vaterite CaCO3 crystals have extensively been studied as drug carriers due to their facile synthesis, biocompatibility, porous structure and pH-sensitive properties.

The work presented in this thesis aims to develop hybrids composed of vaterite and AgNPs for antibacterial coatings. The work focuses on the stabilization of AgNPs, the mechanisms of AgNPs loading and release, the design of antibacterial coatings and the antimicrobial activity of the developed materials against Escherichia coli, methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, three bacteria responsible for numerous nosocomial infections.

Five different capping agents were tested as stabilizing agents for AgNPs: trisodium citrate (Citrate), polyvinylpyrrolidone (PVP), dextran (Dex), diethylaminoethyl–dextran (DexDEAE) and carboxymethyl–dextran (DexCM). The results showed that the capping agents substantially impact the antibacterial activity of the AgNPs. The AgNPs coated with the Dex and DexCM presented the best antibacterial activity due to their better stability which resulted in the release of more silver ions, better interactions with the bacteria and diffusion into the biofilms.

The stabilized AgNPs were then loaded into vaterite via co-precipitation in order to protect, store and control their release, resulting in CaCO3/AgNPs hybrids composed of up to 4% weight content of nanoparticles. The loading mechanism was well-described by the Langmuir adsorption model. The dissolution of CaCO3 was found to be the primary release mechanism at acid pH, while at neutral and basic pH the recrystallisation into non-porous calcite was responsible for the release of AgNPs. The pH-dependent release was then effectively regulated with poly(4-styrenesulfonic acid) to achieve a burst and sustained release. The antibacterial studies demonstrated that the hybrids protect the AgNPs without affecting their antibacterial activity.

Coatings of CaCO3/AgNPs hybrids were designed by a simple drop-casting technique. PVP and mucin were used as additives to control the hybrids distribution, ensure coating mechanical integrity, and prevent the undesired release of AgNPs. Strong antibacterial performance was demonstrated at surface concentration of hybrids between 15 and 30 μg/cm2. The in vitro cytotoxicity studies demonstrated that the hybrids at bactericidal concentrations do not affect the viability of human cells, and in some cases, even decrease the toxicity of AgNPs.

The findings presented in this thesis open new ways to stabilise, protect, store and release AgNPs, shedding light on the release mechanisms of AgNPs from vaterite and helping to foresee the release profiles of other active agents. The developed coating also demonstrates the enormous potential of the hybrids as active components for antibacterial surfaces, crucial to tackling the current antimicrobial resistance crisis.

Item Type:	Thesis
Creators:	Ferreira, A.M.
Date:	February 2023
Rights:	This work is the intellectual copyright of the author. You may copy up to 5% of this work for private study, personal or non-commercial research. Any re-use of the information contained within this document should be fully referenced, quoting the author, title, university, degree level and pagination. Queries or requests for any other use, or if a more substantial copy is required, should be directed in the first instance to the owner of the Intellectual Property Rights.
Divisions:	Schools > School of Science and Technology
Record created by:	Linda Sullivan
Date Added:	25 Jul 2023 09:46
Last Modified:	25 Jul 2023 09:46
URI:	https://irep.ntu.ac.uk/id/eprint/49437