Sustained antimicrobial activity and reduced toxicity of oxidative biocides through biodegradable microparticles.
Sustained antimicrobial activity and reduced toxicity of oxidative biocides through biodegradable microparticles.
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DOI：
10.1016/j.actbio.2017.10.001
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发表时间：
2017-12
影响因子：
9.7
通讯作者：
Day RM
中科院分区：
文献类型：
--
作者：
Sofokleous P;Ali S;Wilson P;Buanz A;Gaisford S;Mistry D;Fellows A;Day RM
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. The manuscript explores a novel approach to utilize the antimicrobial activity of oxidative species for sustained killing of multiple drug-resistant organisms without causing collateral tissue damage. The results demonstrate, for the first time, the ability to load pre-cursor compounds into porous polymeric structures that results in their release and conversion into oxidative species in a controlled manner. Until now, the use of oxidative species has not been considered as a candidate therapeutic replacement for conventional antibiotics due to difficulties associated with handling during manufacture and controlling sustained release without causing undesirable tissue damage. The ultimate impact of the research could be the creation of new materials-based anti-infective chemotherapeutic agents that have minimal potential for giving rise to antimicrobial resistance.
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影响因子：
5
作者：
Makadia HK;Siegel SJ
通讯作者：
Siegel SJ
影响因子：
5
作者：
Celik, E. U.;Turkun, M.;Yapar, A. G. D.
通讯作者：
Yapar, A. G. D.
DOI：
10.1016/s0964-8305(98)00023-7
发表时间：
1998-04-01
影响因子：
4.8
作者：
Denyer, SP;Stewart, GSAB
通讯作者：
Stewart, GSAB
DOI：
10.1016/j.apsb.2014.02.005
发表时间：
2014-04
期刊：
Acta pharmaceutica Sinica. B
影响因子：
--
作者：
Priya James H;John R;Alex A;Anoop KR
通讯作者：
Anoop KR
影响因子：
15.1
作者：
Qi, Lihong;Zuo, Guomin;Zhou, Chaohua
通讯作者：
Zhou, Chaohua