A programmable lipid-polymer hybrid nanoparticle system for localized, sustained antibiotic delivery to Gram-positive and Gram-negative bacterial biofilms
Bacteria enmeshed in an extracellular matrix, biofilms, exhibit enhanced antibiotic tolerance. Coupled with the rapid emergence of multidrug-resistant strains, the current cohorts of antibiotics are becoming ineffective. Alternative antimicrobial approaches are therefore urgently needed to overcome...
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sg-ntu-dr.10356-1056222020-09-21T11:35:13Z A programmable lipid-polymer hybrid nanoparticle system for localized, sustained antibiotic delivery to Gram-positive and Gram-negative bacterial biofilms Baek, Jong-Suep Tan, Chuan Hao Ng, Noele Kai Jing Yeo, Yee Phan Rice, Scott A. Loo, Joachim Say Chye School of Materials Science & Engineering School of Biological Sciences Singapore Centre for Environmental Life Sciences and Engineering Bacterial Biofilms Engineering::Materials Microbial Infection Bacteria enmeshed in an extracellular matrix, biofilms, exhibit enhanced antibiotic tolerance. Coupled with the rapid emergence of multidrug-resistant strains, the current cohorts of antibiotics are becoming ineffective. Alternative antimicrobial approaches are therefore urgently needed to overcome recalcitrant biofilm infections. Here, we propose the use of a non-toxic lipid-polymer hybrid nanoparticle (LPN) system composed of a solid polymer core (i.e. PLGA; poly lactic-co-glycolic acid) and a cationic lipid shell (i.e. DOTAP) for localized, sustained release of antimicrobial agents to bacterial biofilms. LPNs were synthesized through a simple, robust self-assembly approach. LPNs of uniform particle size (i.e. 100–130 nm), efficiently encapsulated (up to 95%) bioimaging molecules or antibiotics and provided controlled release of the latter. The cationic lipid coating enabled the LPN to anchor onto surfaces of a diverse range of Gram-positive and Gram-negative bacterial pathogens, either in the planktonic or biofilm form. Consistently, the LPN formulations reduced more than 95% of biofilm activity at concentrations that were 8 to 32-fold lower than free antibiotics. These data clearly indicate that these novel formulations could be a useful strategy to enhance the efficacy of antimicrobials against planktonic cells and biofilms of diverse species. NRF (Natl Research Foundation, S’pore) MOE (Min. of Education, S’pore) Accepted version 2019-10-25T01:58:35Z 2019-12-06T21:54:43Z 2019-10-25T01:58:35Z 2019-12-06T21:54:43Z 2018 Journal Article Baek, J.-S., Tan, C. H., Ng, N. K. J., Yeo, Y. P., Rice, S. A., & Loo, J. S. C. (2018). A programmable lipid-polymer hybrid nanoparticle system for localized, sustained antibiotic delivery to Gram-positive and Gram-negative bacterial biofilms. Nanoscale Horizons, 3(3), 305-311. doi:10.1039/C7NH00167C https://hdl.handle.net/10356/105622 http://hdl.handle.net/10220/50260 10.1039/C7NH00167C en Nanoscale Horizons © 2018 Royal Society of Chemistry. All rights reserved. This paper was published in Nanoscale Horizons and is made available with permission of Royal Society of Chemistry. 7 p. application/pdf |
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Bacterial Biofilms Engineering::Materials Microbial Infection Baek, Jong-Suep Tan, Chuan Hao Ng, Noele Kai Jing Yeo, Yee Phan Rice, Scott A. Loo, Joachim Say Chye A programmable lipid-polymer hybrid nanoparticle system for localized, sustained antibiotic delivery to Gram-positive and Gram-negative bacterial biofilms |
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Bacteria enmeshed in an extracellular matrix, biofilms, exhibit enhanced antibiotic tolerance. Coupled with the rapid emergence of multidrug-resistant strains, the current cohorts of antibiotics are becoming ineffective. Alternative antimicrobial approaches are therefore urgently needed to overcome recalcitrant biofilm infections. Here, we propose the use of a non-toxic lipid-polymer hybrid nanoparticle (LPN) system composed of a solid polymer core (i.e. PLGA; poly lactic-co-glycolic acid) and a cationic lipid shell (i.e. DOTAP) for localized, sustained release of antimicrobial agents to bacterial biofilms. LPNs were synthesized through a simple, robust self-assembly approach. LPNs of uniform particle size (i.e. 100–130 nm), efficiently encapsulated (up to 95%) bioimaging molecules or antibiotics and provided controlled release of the latter. The cationic lipid coating enabled the LPN to anchor onto surfaces of a diverse range of Gram-positive and Gram-negative bacterial pathogens, either in the planktonic or biofilm form. Consistently, the LPN formulations reduced more than 95% of biofilm activity at concentrations that were 8 to 32-fold lower than free antibiotics. These data clearly indicate that these novel formulations could be a useful strategy to enhance the efficacy of antimicrobials against planktonic cells and biofilms of diverse species. |
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School of Materials Science & Engineering |
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School of Materials Science & Engineering Baek, Jong-Suep Tan, Chuan Hao Ng, Noele Kai Jing Yeo, Yee Phan Rice, Scott A. Loo, Joachim Say Chye |
format |
Article |
author |
Baek, Jong-Suep Tan, Chuan Hao Ng, Noele Kai Jing Yeo, Yee Phan Rice, Scott A. Loo, Joachim Say Chye |
author_sort |
Baek, Jong-Suep |
title |
A programmable lipid-polymer hybrid nanoparticle system for localized, sustained antibiotic delivery to Gram-positive and Gram-negative bacterial biofilms |
title_short |
A programmable lipid-polymer hybrid nanoparticle system for localized, sustained antibiotic delivery to Gram-positive and Gram-negative bacterial biofilms |
title_full |
A programmable lipid-polymer hybrid nanoparticle system for localized, sustained antibiotic delivery to Gram-positive and Gram-negative bacterial biofilms |
title_fullStr |
A programmable lipid-polymer hybrid nanoparticle system for localized, sustained antibiotic delivery to Gram-positive and Gram-negative bacterial biofilms |
title_full_unstemmed |
A programmable lipid-polymer hybrid nanoparticle system for localized, sustained antibiotic delivery to Gram-positive and Gram-negative bacterial biofilms |
title_sort |
programmable lipid-polymer hybrid nanoparticle system for localized, sustained antibiotic delivery to gram-positive and gram-negative bacterial biofilms |
publishDate |
2019 |
url |
https://hdl.handle.net/10356/105622 http://hdl.handle.net/10220/50260 |
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1681058771836600320 |