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Sustained antimicrobial activity and reduced toxicity of oxidative biocides through biodegradable microparticles

Sofokleous, P; Ali, S; Wilson, P; Buanz, A; Gaisford, S; Mistry, D; Fellows, A; (2017) Sustained antimicrobial activity and reduced toxicity of oxidative biocides through biodegradable microparticles. Acta Biomaterialia , 64 pp. 301-312. 10.1016/j.actbio.2017.10.001. Green open access

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Abstract

The spread of antibiotic-resistant pathogens requires new treatments. Small molecule precursor compounds that produce oxidative biocides with well-established antimicrobial properties could provide a range of new therapeutic products to combat resistant infections. The aim of this study was to investigate a novel biomaterials-based approach for the manufacture, targeted delivery and controlled release of a peroxygen donor (sodium percarbonate) combined with an acetyl donor (tetraacetylethylenediamine) to deliver local antimicrobial activity via a dynamic equilibrium mixture of hydrogen peroxide and peracetic acid. Entrapment of the pre-cursor compounds into hierarchically structured degradable microparticles was achieved using an innovative dry manufacturing process involving thermally induced phase separation (TIPS) that circumvented compound decomposition associated with conventional microparticle manufacture. The microparticles provided controlled release of hydrogen peroxide and peracetic acid that led to rapid and sustained killing of multiple drug-resistant organisms (methicillin-resistant Staphylococcus aureus and carbapenem-resistant Escherichia coli) without associated cytotoxicity in vitro nor intracutaneous reactivity in vivo. The results from this study demonstrate for the first time that microparticles loaded with acetyl and peroxygen donors retain their antimicrobial activity whilst eliciting no host toxicity. In doing so, it overcomes the detrimental effects that have prevented oxidative biocides from being used as alternatives to conventional antibiotics.

Type: Article
Title: Sustained antimicrobial activity and reduced toxicity of oxidative biocides through biodegradable microparticles
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.actbio.2017.10.001
Publisher version: https://doi.org/10.1016/j.actbio.2017.10.001
Language: English
Additional information: Published under a Creative Commons Licence (http://creativecommons.org/licenses/by/4.0/).
Keywords: Antibiotics, Antimicrobial agent, Oxidative biocide, Resistance, Thermally induced phase separation
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10025123
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