Nanocarriers with conjugated antimicrobials to eradicate pathogenic biofilms evaluated in murine in vivo and human ex vivo infection models

Acta Biomaterialia
Yong LiuHenk J Busscher

Abstract

Conventional antimicrobials are becoming increasingly ineffective for treating bacterial infection due to the emergence of multi-drug resistant (MDR) pathogens. In addition, the biofilm-mode-of-growth of infecting bacteria impedes antimicrobial penetration in biofilms. Here, we report on poly(ethylene)glycol-poly(β-amino esters) (PEG-PAE) micelles with conjugated antimicrobials, that can uniquely penetrate biofilms, target themselves to bacterial cell surfaces once inside the low-pH environment of a biofilm and release conjugated antimicrobials through degradation of their ester-linkage with PAE by bacterial lipases. In vitro, PEG-PAE micelles with conjugated Triclosan (PEG-PAE-Triclosan) yielded no inadvertent leakage of their antimicrobial cargo and better killing of MDR Staphylococcus aureus, Escherichia coli and oral streptococcal biofilms than Triclosan in solution. In mice, PEG-PAE-Triclosan micelles with conjugated Triclosan yielded better eradication efficacy towards a MDR S. aureus-infection compared with Triclosan in solution and Triclosan-loaded micelles at equal Triclosan-equivalent concentrations. Ex vivo exposure of multi-species oral biofilms collected from orthodontic patients to PEG-PAE-Triclosan micelles, demo...Continue Reading

Citations

Jan 3, 2019·Chemical Society Reviews·Yong LiuHenk J Busscher
May 7, 2020·Journal of Dental Research·H WanP K Sharma
Dec 15, 2018·Advanced Healthcare Materials·Yong LiuLinqi Shi
Sep 22, 2020·Journal of Environmental Science and Health. Part C, Toxicology and Carcinogenesis·Prabin ShresthaTit-Yee Wong
Jan 24, 2019·Frontiers in Chemistry·Saziye Yorulmaz AvsarCornelia G Palivan
Jan 14, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Nitin Chandra Teja DadiHelena Bujdáková
Oct 26, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Yong LiuLinqi Shi
Feb 23, 2021·ACS Applied Materials & Interfaces·Xingyue YangYumiao Zhang
Mar 14, 2021·Colloids and Surfaces. B, Biointerfaces·Yuhan YanChunguang Ren
Aug 10, 2021·Rare Metals·Meng DingShi-Fang Luan
Nov 24, 2020·Biomacromolecules·Shuyue ZhaoAnjie Dong
Sep 4, 2021·Materials Science & Engineering. C, Materials for Biological Applications·Meihui YinHuining Xiao

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